Fpls 12 621276
Fpls 12 621276
Fpls 12 621276
Plant secondary metabolites (PSMs) play many roles including defense against
pathogens, pests, and herbivores; response to environmental stresses, and mediating
organismal interactions. Similarly, plant microbiomes participate in many of the above-
mentioned processes directly or indirectly by regulating plant metabolism. Studies have
shown that plants can influence their microbiome by secreting various metabolites and,
in turn, the microbiome may also impact the metabolome of the host plant. However, not
Edited by: much is known about the communications between the interacting partners to impact
Roberta Marra, their phenotypic changes. In this article, we review the patterns and potential underlying
University of Naples Federico II, Italy
mechanisms of interactions between PSMs and plant microbiomes. We describe the
Reviewed by:
Emilio Guerrieri,
recent developments in analytical approaches and methods in this field. The applications
Istituto per la Protezione Sostenibile of these new methods and approaches have increased our understanding of the
delle Piante (CNR), Italy
relationships between PSMs and plant microbiomes. Though the current studies have
Anwar Hussain,
Abdul Wali Khan University Mardan, primarily focused on model organisms, the methods and results obtained so far should
Pakistan help future studies of agriculturally important plants and facilitate the development of
*Correspondence: methods to manipulate PSMs–microbiome interactions with predictive outcomes for
Jianping Xu
jpxumcmaster@gmail.com;
sustainable crop productions.
jpxu@mcmaster.ca
Keywords: root exudates, SynCom, multi-omics, phytohormones, VOCs, rhizobia, endophytes, pathogens
Yi Cheng
chengyi@caas.cn
important functions such as repelling pests and pathogens, for the detection of a large number (hundreds to thousands)
acting as signals for symbiosis between plants and microbes, of metabolites acquired from a single plant cell (Brader et al.,
and modifying microbial communities associated with hosts 2014). These platforms provide significant advancement for
(Guerrieri et al., 2019). Many PSMs have positive beneficial the discovery of metabolites produced in situ and of the
effects on human health (Ullrich et al., 2019; Fakhri et al., dynamics of interactions between plant and microbial cells at a
2020) and on agriculture production, contributing significantly single-cell level.
to the economy. However, the functions of many PSMs
remain unknown. For example, while many PSMs and protein- Plant Microbiome
metabolite complexes have been identified, the biological roles The microbial communities of plants, also known as the plant
of most have not been verified (Kosmacz et al., 2020). There microbiome (or plant microbiota), are found in the rhizosphere,
have been several excellent reviews summarizing recent studies phyllosphere, and endosphere. These plant microbiomes play
reporting the novel roles of PSMs and emphasizing the important roles in helping host plants develop immunity
importance of functional understanding of the plant metabolome (Stringlis et al., 2018), suppress diseases (Carrion et al., 2019),
(Fang et al., 2019; Kosmacz et al., 2020; Zhou and Pichersky, supply nutrients (Zhang et al., 2019), and protect from biotic and
2020). The studies presented in those reviews have benefited abiotic environmental stresses (de Vries et al., 2020). Over the last
significantly from recent developments in omics technologies 15 years, plant microbiome studies have progressed significantly
such as high throughput DNA sequencing and high-resolution due to the advent of massive parallel sequencing. These studies
mass spectrometry. have helped define different kinds of plant microbiomes and
plant–microbiome interactions, e.g., the epiphytic microbiome,
seed microbiome, core microbiome (CM), synthetic community
Technologies for Analyzing Plant (SynCom), and DefenseBiome (Liu H. et al., 2020). However,
Metabolites these plant microbiomes are not static, they can change in
Plant metabolomics methods have been used for identifying response to environmental stimuli, including both abiotic stresses
functional secondary metabolites and metabolic pathways for and biotic factors. Indeed, there is increasing evidence that the
both basic and applied research. Those methods help provide structure of plant microbiomes is the result of a series of forward
comprehensive perspectives on how plant metabolic networks and backward interactions between the plant, the microbes
are regulated. The most widely used methods include gas and their environmental physical and chemical conditions. For
chromatography (GC) -mass spectrometry (-MS) (GC-MS), example, PSMs secreted by roots are important mediators of
liquid chromatography-MS (LC-MS), capillary electrophoresis- plant–soil microbiome interactions (Sasse et al., 2018). In maize,
MS (CE-MS), nuclear magnetic resonance spectroscopy (NMR), secondary metabolites such as benzoxazinoids, were shown to
Fourier transform-near-infrared (FT-NIR) spectroscopy, MS attract bacteria Chloroflexi and influence the assembly of the
imaging (MSI), and live single-cell -MS (LSC-MS). These maize microbiomes that subsequently enhance the capacity of
methods are often used in combination because they can provide maize plants to adapt to their environments (Hu et al., 2018).
largely complimentary information with each other by analyzing Among the plants analyzed so far, model species such
different types of metabolites. A number of excellent technical as Arabidopsis thaliana and Echinacea purpurea have been
reviews (Lu et al., 2017; Tahir et al., 2019) and detailed protocols extensively studied to help define their microbiomes and the roles
(Zhalnina et al., 2018) regarding the utilization of these analytical of these microbiomes in enhancing the growth and reproduction
tools in metabolomics experiments have been published. of host plants (Kudjordjie et al., 2019; Maggini et al., 2020).
Most traditional studies of PSMs utilize extracts of However, despite the growing number of studies and reviews
representative plant tissues as the main materials representing demonstrating that different host plants species (Compant et al.,
average plant cells in a specific tissue or organ (Masuda et al., 2019), their development stages (Schlechter et al., 2019), their
2018). Because of the bulk nature of those samples, it is often root exudates (Sasse et al., 2018; Vives-Peris et al., 2020), and
difficult to distinguish between PSMs produced by either host their rhizodeposits (Tian et al., 2020) can all influence the
plants or their associated microbes. However, at present, there composition of the plant microbiomes and their functional
is a growing interest in narrowing PSMs analyses down to the capacities, relatively few reviews have attempted to integrate
single-cell level, allowing the separation of plant cells from the chemical basis and molecular mechanism into the PSMs-
their potentially associated microbial cells. Such separations and microbiome relationship. Complicating the understanding is that
individualized analyses can be achieved using approaches such the relationship is a dynamic one, involving multiple back-and-
as MSI (Boughton and Thinagaran, 2018), matrix-assisted laser forth exchanges of chemical signals and molecular pathways.
desorption ionization (MALDI) and laser ablation electrospray For example, some microbes can modulate the production of
ionization (LAESI) (Etalo et al., 2018a; Bhattacharjee et al., PSMs, including plant bioactive phytometabolites that in turn
2020), live single-cell mass spectrometry (LSC-MS) (Masuda can influence the microbiome (Mastan et al., 2019). Furthermore,
et al., 2018), nanospray desorption electrospray ionization while a number of studies have provided insights into the
mass spectrometry (Nano-DESI MS) (Battin et al., 2016), and structure and dynamics of the plant microbiome, relatively
the spatial metabolomics pipeline (metaFISH) (Geier et al., little is known about the contribution of plant microbiomes to
2020). In combination with MS data alignment and molecular host PSMs. The latest models of traditional medicinal PSMs–
networking software and relevant databases, these tools allow microbiome interactions approaches provide a new framework
for understanding the various types of interactions between PSMs keywords for database searches: a variety of plants (such as
and microbiomes (Maggini et al., 2020). Such an understanding legume plants, medicinal plants), plant microbiome (microbiota),
can have significant impacts on several applied fields such as metagenome, metagenomic, amplicon sequencing, PSMs,
crop cultivation and breeding. During crop breeding, scientists metabolomics, metabolomic analytical methodology, plant
typically select for higher yield and/or better nutrition but only metabolome databases, correlation relationship, metabolomic-
from the crop cultivar perspective with limited consideration microbiome, and omics etc. The main retrieval databases were
of the plant microbiome or the PSMs–microbiome interactions. Web of Science, PubMed, and ResearchGate. Table 1 shows a few
Understanding of the interactions between PSMs and plant common terms and their definitions used in this review.
microbiomes could help opening up a new avenue of research in
crop production. Data Analyses Tools for Association
Over the past few years, the characterization of the plant
Studies Between Plant Metabolome and
microbiomes and their relationships with the host plants using
high-throughput techniques including genome and metagenome Microbiome
sequencing has become a hot topic in research. Both the Due to advances in high-throughput sequencing techniques,
culturome (all microbes that can be cultured in the lab) direct analyses of microbial communities in their natural
and metagenome sequencing techniques are providing in- environments have become increasingly convenient and cost
depth information of the plant microbiome. The culturome is effective. In recent years, microbiome studies using multi-omics
an important component of the microbiome. To obtain the approaches have greatly deepened our understanding of the
culturome, the culturable cells in the microbial community are relationship between microbiomes and hosts. For example, multi-
selected using solid media or liquid medium in high throughput omics studies of the gut microbiome and the human metabolome
formats. Subsequent shotgun sequencing allows the identification (Chen M. X. et al., 2019; Ilhan et al., 2020) have provided new
of linkages between taxonomic identity to important functions understanding in human health and diseases. In order to help
to the cultured cells, such as biological nitrogen fixation. the application of multi-omics technologies on plant metabolome
However, culture-based methods are usually less sensitive than and microbiome studies, we reviewed the data integration and
direct amplicon sequencing for identifying rare microbes. High-
throughput sequencing of specific gene amplicons is typically
more powerful for elucidating the composition, and spatial TABLE 1 | Common terms and definitions.
distribution of microorganisms in their environments and this
Term Definition
approach is increasingly used in plant microbiome studies. The
metagenome approaches can be combined with other high- Secondary metabolism Metabolic pathways and their associated small
throughput methods, such as metabolomics, proteomics, and molecular products that are non-essential for the
growth and reproduction of the organism
transcriptomics. There is an excellent review discussing the
Rhizosphere All microorganisms found in the narrow region of soil or
quality of publicly available genome data, metagenome data, microbiome substrate that is directly influenced by root secretions
other omics data, and software pipelines for analyzing such data and associated soil, also called root microbiome
(Lucaciu et al., 2019). In these analyses, it’s important to minimize Epiphytic microbiome All microorganisms found on the surface of aerial parts
sequence artifacts and reduce noise in data (Davis et al., 2018; of plants. These microorganisms use plants for physical
Zhou et al., 2019). For processing the bacterial 16S rRNA gene support but do not obtain any nutrients from plants nor
cause any damage or offer any benefit to host plants.
and fungal ITS amplicons, a collection of software, such as QIIME
Endophytic microbiome All microorganisms found inside the internal tissues of
(Caporaso et al., 2010), UPARSE (Edgar, 2013), VSEARCH
plants, including both aerial and root tissues
(Rognes et al., 2016), PIPITS (Gweon et al., 2015), and USEARCH
Seed microbiome All microorganisms found on the surface of and inside
(Edgar and Flyvbjerg, 2015) have been developed. Similarly, for the seeds
shotgun microbiome sequencing analyses, several recent articles Core microbiome The group of microorganisms that are found in all
reported specific computational workflow and bioinformatics individuals of a host species. The persistent association
resources (Liu Y. X. et al., 2020), including Microbiome Helper suggests a potentially critical function within the
(Comeau et al., 2017), HmmUFOtu (Zheng et al., 2018), iMicrobe ecological niche of the host in which these
microorganisms are found
(Youens-Clark et al., 2019), MMinte (Mendes-Soares et al., 2016),
Synthetic community Defined systems with reduced complexity for both the
MDiNE (McGregor et al., 2020), MicrobiomeAnalyst (Dhariwal
(SynCom) host and the microorganisms. SynCom serves as
et al., 2017), SIMBA (Mariano et al., 2016), and iMAP (Buza model systems to investigate the performance and
et al., 2019). Several in-depth summaries and comparisons of stability of microbial communities or to identify the
next-generation amplicon sequencing and analyses approaches necessary conditions for generating interaction patterns
were published recently (Lucaciu et al., 2019; Nilsson et al., 2019). and higher order community structure and function
Herein, we review the current literature on the bidirectional DefenseBiome Plant-associated microbes that are positively
associated with plant stress resistance
interactions and effects between PSMs and plant microbiomes.
Rhizodeposits All material transferred from plant roots to the soil. They
In addition, we review the latest advances in plant metabolome include dead root tissues and cells, root exudates (both
analytical technologies and methods for analyzing the soluble and insoluble materials), and gasses such as
relationships between the plant metabolome and the plant CO2 and ethylene.
microbiomes. To achieve our objectives, we used the following Culturome All microbes in a sample that can be cultured in the lab.
analysis methods for studying human and animal microbiomes drivers of metabolic variations. A commonly used method
and metabolomes; and provided a few suggestions on how they to infer the drivers of metabolic variations in a network is
could be used for plant studies. Table 2 lists the methods and tools correlation analysis, such as Pearson’s and Spearman’s correlation
for association studies between metabolome and microbiome. coefficients among all pairs of operational taxonomic units
Correlation-based analysis of paired microbiome-metabolite (OTUs) and the metabolite profiles. An interaction between
data sets has been a common approach to identify microbial microbes is inferred when there is a high correlation coefficient
TABLE 2 | Comparison of methods and tools for association studies between metabolites and microbiomes.
Univariate analysis Pearson Comparatively simple method, but high false positive rate, Multiple calibration tests Mao et al., 2016; Ilhan et al.,
Spearman unable to explain biological mechanism are required 2020
Common descending PCA A multivariable correlation analysis method to describe the van der Kloet et al., 2016
dimension methods PLS relationship between the two data matrices.
Joint and individual JIVE An extension of PCA, identifying joint variations in multiple Lock et al., 2013
variation explained data types, reducing the dimensionality of data and
determining the unique features of a particular data type.
Simultaneous SCA DIStinct COmmon SCA (DISCO-SCA) offers new avenues Smilde et al., 2017
component analysis for multi-omics data fusion
Canonical correlation CCA Samples over variables, Sparse CCA, kernel CCA and Multivariable analysis Kostic et al., 2015
RCCA partial least-squares
Procrustes analysis PA Powerful least-square approach, simplifies omics McHardy et al., 2013
comparisons, may not be sufficient to draw conclusions
Co-inertia analysis CIA Suitable approach to determine the relationship, not Hill et al., 2017
suitable for large-scale data analysis
Maximum information MIC MINE statistics for identify associations and characterize http://exploredata.net Reshef et al., 2011
coefficient such as non-linearity and monotonicity, comes closer than
mutual information.
Linear regression LR Provide more accurate results Bakker O. B. et al., 2018
Generalized coRrelation GRaMM Captures linear/non-linear correlations in datasets and can https: Liang et al., 2019
analysis adjust the influence of confounders, combines LR, MIC //github.com/chentianlu.
et al.
Seed set framework A TDA Calculate the symbiosis and competition scores of different Greenblum et al., 2012
microbes and predict the interaction relationship between
microbes.
Predicted relative PRMT Explore metabolite-space inferred from the metagenome, http://camera.calit2.net Larsen et al., 2011
metabolic can combine and analyze additional metagenomic and
Turnover metabolic datasets
Computational MIMOSA2 Mechanistic interpretation and hypothesis generation. Only www.borensteinlab.com/ Noecker et al., 2016
framework analyze metabolites in the specific reference database software_MIMOSA2.html
Genome-scale GEMs Contains a complete metabolic map of all metabolic Magnúsdóttir et al., 2017
metabolic models reactions of the body and can be used for metabolite.
Integration of Histology and Metagenomics Data
Neural networks Mmvec Estimate probability and strength of interaction https://github.com/ Morton et al., 2019
biocore/mmvec)
A Valid Alternative to Proportionality Present proportionality as a means to analyze related data. Lovell et al., 2015
Correlation
Correlation inference for CCLasso An alternating direction algorithm from augmented https://github.com/ Fang et al., 2015
Compositional data Lagrangian method. Poorly for the hub model, component huayingfang/CCLasso
through Lasso fraction estimation
Sparse Correlations for SparCC Not rely on high diversity. Relies on reliable component https://bitbucket.org/ Friedman and Alm, 2012
Compositional data counts, no considered for the overall property yonatanf/sparcc
SParse InversE SPIEC-EASI Making assumptions about the underlying network http://bonneaulab.bio. Kurtz et al., 2015
Covariance Estimation structure. nyu.edu/
Scale-free structures elude accurate inference
Correlation network CCREPE (bioBakery or ReBoot) Provides a similarity measure more http://huttenhower.sph. Faust et al., 2012; McIver et al.,
appropriate for compositional data analysis, performance is harvard.edu/ccrepe 2018
similar to SparCC
Multivariate statistical M2 IA Integrative data analysis from data preprocessing, univariate http://m2ia.met- Ni et al., 2020
analyses and multivariate statistical analyses, advanced functional bioinformatics.cn
analysis for biological interpretation, to a summary report.
between them (Morton et al., 2019). However, traditional Stress Response, and Plant Invasion”). We finish by discussing
correlation analyses, such as univariate analysis and simultaneous potential areas for future research.
component analysis that treat the observed data as absolute
abundances of the microbes, may lead to spurious results. This is
because most of the observed data through metagenomic analyses
only represent relative abundances (Gevers et al., 2014). For
EVIDENCE AND MODEL FRAMEWORK
example, concluding that a microbial community showing no FOR INTERACTIONS BETWEEN PLANT
signs of microbiome–metabolite interactions based on a single SECONDARY METABOLITES AND
correlation analysis is unlikely correct, as none of the traditional PLANT MICROBIOMES
tools can definitively identify actual correlations (Weiss et al.,
2016). Consequently, simple correlation analysis alone is not As shown by Köberl et al. (2013), the same plants grown
suitable for detecting true microbial contributors to metabolite in different locations may produce different SMs, with some
variations. Thus, special care and appropriate adjustments are of the differences attributed to their associated microbes at
required prior to correlation analysis for microbiome and different sites. Microbes adapted to specific locations and
metabolome data (Fang et al., 2015). Recent methods such associated with specific plants may produce unique effects on
as MIMOSA2, Correlation inference for Compositional data host plants, including the production of SMs (Huang et al.,
through Lasso (CCLasso), Neural networks (such as mmvec), 2018). For example, Methylobacterium was found to be involved
Predicted relative metabolic turnover (PRMT), Compositionally in modulating the production of phytometabolites associated
Corrected by REnormalization and PErmutation (CCREPE), and with flavor and in metabolizing plant host compounds, including
Sparse Correlations for Compositional data (SparCC) (Table 2) volatile organic compounds (VOC) (Brader et al., 2014). Indeed,
have been designed to take these compositional biases into the induction of PSMs by endophytes may be a very general
account for analyzing microbiome–metabolite interactions. The phenomenon in aromatic and medicinal plants. For example,
joint usage of multiple methods can achieve better results. several studies have shown that root exudates containing
Several tools and resources are described in Figure 1 and the compounds such as aromatic organic acids (nicotinic, shikimic,
following subsection. salicylic, cinnamic, and indole-3-acetic acids) could shape the
Parallel approaches can offer new opportunities for analyzing root microbiome (rhizobiome), which subsequently influenced
microbiome–metabolite interactions especially if diverse types of root–microbe interactions (Sasse et al., 2018; Cotton et al., 2019).
information can be integrated. However, such data integration The combinations of plant exudation and microbial nutrient
and analysis methods are still in their early stages of development traits could interact to produce unique microbial community
(Lamichhane et al., 2018). In addition, to understand the assemblies (Zhalnina et al., 2018). These studies have led to
underlying biological processes for the observed patterns of a proposed framework for studying the relationship between
interaction, it is important to develop computational approaches microbiome and PSMs, as depicted in Figure 2.
that include individual organisms’ unique biological features Interactions between legume plants and their rhizobia
(Mallick et al., 2019). With a growing interest in connecting the represent among the best studied models of PSMs-microbe
microbes and metabolites in the context of plant and human interactions. Besides being economically important crops for
health, we also need to bring together researchers from the food and forage, legume plants (such as pea, soybean, peanuts,
two domains that traditionally do not interact with each other clover, and alfalfa) and rhizobia have been used for decades
(Misra, 2020). for revealing how secondary metabolites from both partners
Importantly, while there are limitations in the correlation- mediate their interactions to establish root nodules for biological
based analysis to identify key microbiome-metabolite links, nitrogen fixation. Previous studies have observed a higher
such linkages can be found in the current microbiome- abundance of symbiotic rhizobia in the root microbiome
metabolome data (Noecker et al., 2019). As is commonly stated, of legume plants (70% with clover Trifolium) than that of
a correlation doesn’t mean a causation or a true biological bulk soil or the root microbiome of other plants (Hartman
interaction. However, statistically significant correlations do help et al., 2017; Zhang et al., 2018). Soybean (Glycine max) is an
generate hypotheses and guide experimental efforts. Indeed, example of legume plants that has been studied extensively
appropriately designed and carefully executed experiments are for its mutualistic relationships with nitrogen-fixing rhizobia
indispensable for confirming the hypotheses about the role of and arbuscular mycorrhizal fungi. Soybeans secrete various
specific metabolites in plant–microbiome interactions. In the specialized metabolites such as isoflavones and saponins into the
sections below, we first describe evidence for and a general model soil (Sugiyama, 2019). Specifically, isoflavones and strigolactones
of PSMs–plant microbiome interactions. We then use specific are signal molecules for symbioses between soybean with
examples to show how PSMs influence plant microbiomes rhizobia and arbuscular mycorrhizal fungi, respectively. During
(see section “Evidence for Specific PSMs Modulating the Plant symbiosis, a hallmark feature of legume plants is that their roots
Microbiome”) and how plant microbiomes influence PSMs (see secrete flavonoids/isoflavones [such as condensed tannins (CTs,
section “Plant Microbiomes Contribute to the Productions of prodelphinidins and procyanidins), daidzein and genistein)] into
PSMs”). We then describe how the PSMs–plant microbiome the rhizosphere as signal compounds to attract nitrogen-fixing
interactions could be used for crop production (see section bacteria such as Ensifer (formerly Sinorhizobium), Rhizobium,
“PSMs–Microbiome Interactions Impact Crop Breeding, Abiotic Allorhizobium, Mesorhizobium, Neorhizobium, Azorhizobium,
FIGURE 1 | Reference of schematic workflow for plant secondary metabolomics-microbiome discovery projects. Some information and pictures are adapted from
Lavelle and Sokol (2020).
FIGURE 2 | Factors influencing the interactions between plant secondary metabolites and plant microbiomes.
Pararhizobium, and Bradyrhizobium (Hartman et al., 2017). while root exudates from maize promoted faba bean nodulation
Similarly, bacteria in the genera Cupriavidus, Paraburkholderia, (flavonoids), root exudates from wheat and barley did not
and Trinickia also form mutualistic interactions with (Li et al., 2016). Recently, an interesting study suggested that
Papilionoideae and Caesalpinioideae to establish nodulation. The cyanide production by cassava (Manihot esculenta Crantz) can
analysis of rhizosphere microbiomes between plants with and trigger ethylene production in adjacent peanut (Arachis hypogaea
without isoflavone synthetase revealed that isoflavones exerted L.) roots (Chen Y. et al., 2020), which subsequently changed
significant influence on the abundance of Xanthomonadaceae the microbial composition and re-assembled the microbial
and Comamonadaceae (White et al., 2017). In addition, a recent co-occurrence network of peanut plants, causing an increased
study indicated that daidzein had a significant effect on soybean abundance of Catenulispora spp., an actinobacterium. However,
root microbiome, showing a concentration-specific effect on the full details of this specific relationship between legume plants
the bacterial community assemblage (Okutani et al., 2020). and rhizobia remain to be elucidated.
Specifically, the results suggested that daidzein functions both Apart from impacting legume and bacterial interactions,
as an attractant and a repellent for different groups of bacteria. flavanones (such as strigolactones) can positively influence the
When the concentration of daidzein is high in the rhizosphere, growth of ectomycorrhizal fungi and increase the colonization of
there is an increased abundance of Comamonadaceae while AM fungi. For example, flavanones can enhance the germination
rhizobia abundance was decreased, causing an overall reduced of spores of ectomycorrhizal fungi in genera Pisolithus and
α-diversity. The overall reduced microbial diversity was probably Suillus as well as stimulate the production of symbiotic effector
because daidzein is not a preferred carbon source of rhizobia, protein in the mushroom Laccaria bicolor (Garcia et al., 2015;
different from several other bacteria that were enriched in Pei et al., 2020). In contrast, the suppression of flavonoids and
daidzein-treated soils. In addition, a study showed that root– phenylpropanoid pathway secretion reduced the endophytes and
root interactions between the broad bean (Vicia faba) and ectomycorrhizal colonization of the maize and poplar roots,
maize significantly increased both nodulation and symbiotic respectively (Mehmood et al., 2020). At present, the mechanisms
N2 fixation in intercropped V. faba (Li et al., 2016). However, of their interactions remain unclear.
EVIDENCE FOR SPECIFIC PSMs (Stringlis et al., 2018, 2019). Further experiments showed that
MODULATING THE PLANT one specific coumarin compound called scopoletin inhibited
the growth of soilborne pathogens whereas rhizobacteria were
MICROBIOME not affected. This was further confirmed by evidence showing
that coumarins could shape the composition of a SynCom,
Plants exude both low-molecular-weight compounds (such as
where the abundance of Pseudomonas was significantly higher in
phenolics, amino acids, nucleotides, sugars, terpenoids, and
coumarin-deficient Arabidopsis f6’h1 mutants than in wild-type
lipids) and high-molecular-weight compounds (such as nucleic
plants (Voges et al., 2019). A recent excellent review described
acids, polysaccharides, and proteins). The types of compounds
coumarins as the “new kids on the block” in the chemical
and their relative abundances depend on the species of plants,
communications between plant roots and root microbiomes
their growth and developmental stages, and presence of stress
(Stassen et al., 2020).
(abiotic, biotic) factors (Korenblum et al., 2020). The key classes
Recent studies found that benzoxazinoids (BXs), SMs
of PSMs are either non-volatile compounds or VOCs. Plant
produced by several Poaceae species, and several downstream
roots secrete PSMs into the rhizosphere and/or soil environment
metabolites, could act as allelochemicals and natural pesticides
actively using ATP as the energy source and passively through
on the root microbiome (Hu et al., 2018; Cotton et al., 2019;
diffusion. PSMs are also released when root tissues and cells are
Kudjordjie et al., 2019; Schütz et al., 2019; Jacoby et al., 2020).
detached from roots. After entering into the rhizosphere and
Specifically, Hu et al. (2018) used a benzoxazinoids deficient
soil, most PSMs may be quickly utilized by soil microbes, but
maize mutant bx1 and found that different bacterial and fungal
some can remain in the rhizosphere and mediate interactions
communities were assembled in the roots of the mutants
among organisms (Sugiyama and Yazaki, 2014). The roles
compared to wild-type maize. Another research used different
of root exudates in plant–microbe chemical interactions in
maize BX mutant materials (BX knockout mutants, bx1, bx2, and
the rhizosphere is increasingly recognized (Sasse et al., 2018;
bx6, and their near-isogenic W22-based controls T43 and a1 -m3 ),
Yuan et al., 2018; Williams and de Vries, 2020). Furthermore,
and found similar results (Kudjordjie et al., 2019). Interestingly,
different rhizodeposits can influence the rhizosphere microbiome
such effects could be detected over several generations of
composition differently (Pascale et al., 2020). Some root PSMs
the maize crop, suggesting that these molecules are likely
can affect the assembly of the root microbiome even before
key agents in plant–soil microbe feedback interactions (Jacoby
microbes reach the root surface (Sasse et al., 2018). Recent studies
et al., 2020). Overall, benzoxazinoids enriched Methylophilaceae
showed that selected SMs including coumarin, triterpenes,
bacteria while repressed Xanthomonadaceae (Cotton et al., 2019),
flavonoid, benzoxazinoid, and phytohormones can impact the
likely due to their differential ability to use benzoxazolinones as
proliferation or suppression of specific microbes around the root
carbon and energy sources (Schütz et al., 2019).
of host plants (Holmer et al., 2017; Hu et al., 2018; Chen Q. et al.,
Similar to the benzoxazinoids, camalexin, an indolic
2019; Voges et al., 2019; Chen Q.-L. et al., 2020). These results call
compound, can also modulate the functionality of root
for further investigations into how natural habitat variation, crop
microbiome (Koprivova et al., 2019). Loss of function of
genetic variation, and plant introduction between locations can
CYP71A27, a root-specific gene involved in the synthesis of
potentially affect the PSMs and the recruitment and assembly of
camalexin, affected not only the soil microbiome but also led
plant microbiome.
to the loss of plant growth-promoting effect by Pseudomonas.
However, loss of the growth-promoting effect in the CYP71A27
Coumarin, Benzoxazinoid, Terpenes, and mutants could be complemented chemically by the addition of
Other Root-Exuded Molecules Modulate camalexin. Taken together, these results suggested camalexin’s
Root Microbiome beneficial effects on plants by mediating the interaction between
Plant secondary metabolites capable of changing plant plant roots and microbes (Koprivova et al., 2019).
microbiomes belong to diverse classes, including phenolics, Terpenoids are a major component of the root-specialized
benzoxazinoids, terpenes, and alkaloids (Cotton et al., metabolites. They contribute to the assembly of Arabidopsis-
2019; Voges et al., 2019; Wang and Niu, 2019). Non-volatile specific root microbiome by regulating the growth of specific
compounds such as coumarins and flavonoids are produced root bacteria (Wang and Niu, 2019). One group of terpenoids
by many plant species and are common in the rhizosphere. is the triterpenes, synthesized via the mevalonate pathway that
Coumarins are a family of plant-derived SMs produced via can accumulate in plant tissues as triterpene glycosides (Pascale
the phenylpropanoid pathway, and are involved in responses et al., 2020). Recent experiments investigated the effects of
of dicotyledonous plants to iron deficiency (Stringlis et al., triterpene and sesterterpene biosynthesis on Arabidopsis root
2019). Recent studies suggested that coumarins, a sub-group of microbiome assembly. The results showed that the compositions
phenolic compounds, can influence the rhizosphere microbiome of the root microbiome communities of the triterpene and
composition and exhibit differential toxicity against beneficial sesterterpene biosynthesis mutants were significantly different
and pathogenic microorganisms (Lundberg and Teixeira, from those of the wild-type plants (Chen Q. et al., 2019; Huang
2018; Voges et al., 2019). For example, a coumarin-deficient et al., 2019). The authors further investigated whether triterpenes
Arabidopsis mutant with beta-glucosidase gene BGLU42 regulated Arabidopsis root bacteria using purified triterpene
knocked out showed an increase in the relative abundance of compounds. Growth assays of selected microbial strains
Proteobacteria and a decrease of Firmicutes around its root showed that purified triterpenes stimulated the proliferation
of Arenimonas while inhibited the growth of Arthrobacter addition, another recent study found that the attraction of certain
(Huang et al., 2019). bacteria with antifungal properties through soil toward roots
Some of the known PSMs have potent antibiotic activities. could be stimulated by VOCs (e.g., propanal, γ-nonalactone, and
Plants secreting such compounds may create additional dimethyl disulfide) produced by Carex arenaria roots, with the
constraints on the groups of bacteria that can grow in the cell numbers of Janthinobacterium, Collimonas, and Paenibacillus
specific plant microbiome (Huang et al., 2018). For example, increased by up to three times higher as compared to those in
flavonoids have potent antimicrobial activity against a wide the control soil samples without C. arenaria (Schulz-Bohm et al.,
range of pathogenic microorganisms in vitro (Górniak et al., 2018). However, the soil microbes were not equally attracted by
2019). In addition, some PSMs such as flavonoids are not only VOCs to colonize plant roots.
associated with the regulation of symbiosis between plants Due to their antimicrobial effects and their potential role
and microbes (e.g., arbuscular mycorrhizal, ectomycorrhizal, as carbon sources, plant VOCs can play significant roles in
rhizobial, and actinorhizal symbioses), but also as quorum- determining the characteristics of the microbiome on the above-
sensing (QS) inducers for communications among microbes. ground plant surfaces (including stems, leaves, flowers, and
Different legumes produce unique flavonoids that bind to specific fruits). A recent study found that mutation in CYP706A3, a
NodD proteins on the surface of rhizobia strains and species to clustered terpene synthase and a cytochrome P450 encoding
regulate their symbiosis (Holmer et al., 2017). Application of 7, gene, suppressed sesquiterpene and monoterpene emissions in
40 -dihydroxyflavone, the most abundant flavonoid in the root Arabidopsis flowers and changed the floral microbial OTUs in
exudate of Medicago sativa, to bulk soil caused significant changes the genus Pseudomonas (Boachon et al., 2019a). This study
of the relative richness of Acidobacteria (increased), Gaiella, suggested that the CYP706A3-generated soluble metabolites
Nocardioidaceae, and Thermomonosporacea (reduced). These played a role in the assembly of specific bacterial taxa colonizing
microbes are known to interact with plant roots (Szoboszlay Arabidopsis flowers. Furthermore, the floral microbiome may
et al., 2016). Similarly, catecholic coumarins, benzoxazinoid, contribute to VOC productions, thereby inducing or reducing
terpenes, jasmonate, indole glucosinolates, daidzein and others the emission of VOCs, and potentially catabolize others.
compounds also have antibacterial activity (Maggini et al., 2018; The results suggested that bacteria belonging to the genera
Rajniak et al., 2018; Dubey et al., 2020). Decades of research Staphylococcus, Bacillus, and Sphingomonas could exploit certain
have demonstrated that a large number of secondary metabolites plant VOCs as carbon source, which may reduce their emission
are involved in plant defense response to pathogens (Wang rates (Helletsgruber et al., 2017). These bacterial groups
et al., 2020). Indeed, some of these PSMs have been used in contribute to floral scent differences among flowers. One study
antimicrobial scaffolds (Trda et al., 2019). There is increasing found that in bee-pollinated Penstemon digitalis, the nectar
interests in mining bioactive compounds from economic crops volatile linalool could slow the growth of bacteria across
such as garlic and ginger who are rich in allicin and curcumin the P. digitalis phyllosphere (Burdon et al., 2018). Another
etc. as natural antimicrobial compounds in healthy foods. recent study showed that β-caryophyllene in tomato leaves can
act as a signature VOC, which can lead to the release of
a large amount of salicylic acid (SA) from adjacent tomato
Volatile Organic Compounds From roots, and contribute to their similar rhizosphere microbial
Plants Modulate Plant Microbiome communities (up to 69%) (Kong et al., 2020). Together, these
Apart from soluble secondary metabolites mentioned above, studies show that the plant VOC-microbiome interactions are
plants also release various VOCs which constitute an estimated widespread and are of great ecological interests. A recent
1% of PSMs (Venturi and Keel, 2016). Due to their unique review provided an excellent account of the interaction between
physico-chemical properties, VOCs can easily diffuse through the phyllosphere or rhizosphere microbiomes and plant VOC
gas- and water- filled pores in the soil and can, therefore, have a emissions (Schenkel et al., 2019).
broad effective range in soil (Schulz-Bohm et al., 2018), including
mediating interactions with surrounding soil microorganisms.
Examples of major plant VOCs include aldehydes, terpenoids, Phytohormones Modulate the Plant
phenylpropanoids, and common monoterpenes limonene, Microbiome
β-pinene, benzenoids, and β-caryophyllene. Many of these Phytohormones are an integral part of the plant defense system,
VOCs have antimicrobial properties and can strongly influence commonly known as the plant’s systemic acquired resistance
plant microbiomes, including that on the plant phyllosphere (SAR) and induced systemic resistance (ISR). Phytohormones
(Farré-Armengol et al., 2016). A recent study evaluated the are a class of small bioactive molecules (Chen X. et al., 2020).
antimicrobial and anti-quorum sensing (QS) properties of 29 In addition to regulating plant physiological and morphological
common essential oil compounds from plants. Twenty-two of responses, phytohormones also impact the plant microbiome.
these 29 compounds were identified to have QS-inhibitory ability, Phytohormones known to influence plant microbiomes include
while seven promoted the QS to a variable extent in populations SA, jasmonic acid (JA), ethylene (ET), abscisic acid (ABA), and
of two bacteria Chromobacterium violaceum and Pseudomonas strigolactones (SL). Below we briefly review these findings.
aeruginosa (Peter et al., 2019). These results suggested that The first study on the potential effect of SA on the phyllosphere
QS-inhibitory compounds of natural plant origins could be microbiome examined an SA mutant of Arabidopsis thaliana
used to formulate a new generation of antimicrobial agents. In and found limited difference in the phyllosphere microbiome
between the SA mutant and the wild-type (Bodenhausen et al., Different phytohormones induce different effects on plant
2014). However, a different study found SA to be capable microbiomes. ABA is a common phytohormone and the
of modulating the root microbiome of A. thaliana (Lebeis exogenous application of ABA caused a preferential selection for
et al., 2015). Specifically, plants with altered SA signaling microbes in the genera Limnobacter, Massilia, and Cellvibrio in
had root microbiomes that differed from each other in a potting soil mixture (Carvalhais et al., 2014). Strigolactones
their relative abundance of Proteobacteria, Koribacteraceae, (SL) are commonly exuded from roots under phosphate or
Intrasporangiaceae, Kineosporiaceae, Micromonosporaceae, nitrogen starvations to attract AM fungi, and their biosynthesis
Nocardioidaceae as well as the core microbiome when compared are downregulated after colonization of AM fungi. In contrast,
with those of wild-type plants. The study further showed SA, ET, and gibberellins (GA) can all inhibit both AM and
that different bacterial strains responded to SA in different root nodule symbiosis (Rodriguez et al., 2019). A recent study
ways, either as a growth signal or as a carbon source, which found that SL-mediated metabolic pathways are likely involved
in turn affected the root microbiome. While the induction of in the regulation of root microbiome in rice. In SL deficient
SA-mediated defenses reduced endophytic bacterial community mutants, there was a higher bacterial richness and a lower fungal
diversity in Arabidopsis (Kniskern et al., 2007), certain members diversity than the wild-type plants (Nasir et al., 2019). In addition,
of the endophytic microbiome showed evidence of SA-related certain beneficial bacteria, including those in Nitrosomonadaceae
dependence for successful colonization. One study showed that and Rhodanobacter, were significantly decreased in SL mutants
in wheat, SA caused changes in microbiome through allelopathy compared to the WT (Nasir et al., 2019). Two recent reviews
(Kong et al., 2018). summarized the relevant research progress of ABA and SL as
Similarly, the effects of JA on plant microbiome are also regulators of plant–microbiome interactions (Shtark et al., 2018;
evident. One study suggested that JA signaling was involved in Nasir et al., 2020).
controlling the density of Azoarcus endophyte, thereby shaping Plant microbiomes contain many beneficial and pathogenic
the beneficial microbiome in rice roots (Chen X. et al., 2020). microbes. Overtime, plants have evolved mechanisms to
The activation of JA-dependent defense mechanisms led to recognize these microbes and correspondingly reprogram
suppression of the SA-mediated defenses against the hemi their defenses to enable or limit the colonization of specific
biotrophic pathogen P. syringae pv. tomato (Wasternack and microbes (Zhou et al., 2020). Apart from the pathways
Hause, 2013). However, the addition of external methyl-JA specific for phytohormones, the different phytohormone
also affected the root microbiome of A. thaliana (Carvalhais signaling pathways are interconnected at the molecular
et al., 2013) and wheat (Liu et al., 2017). Here, JA acted and phenotypic levels (Rodriguez et al., 2019). Some
as a SAR inducer in leaves to impact both the phyllosphere of the phytohormones act antagonistically with each
and endophytic microbiomes. Apart from JA, derivatives of other, potentially enabling certain microbes to exploit
JA are also capable of influencing the plant root microbiome such antagonism to evade host defense and facilitate
(Carvalhais et al., 2017; Sasse et al., 2018). Compared with their own colonization (Jha et al., 2018). During this
the wild-type, Arabidopsis mutants with JA signaling pathway dynamic interactions, the plant microbiome may also
defects showed lower amounts of asparagine, ornithine, and develop resistance to PSMs (Chen Q.-L. et al., 2020).
tryptophan, as well as increased abundance of Streptomyces, There is an increasing interest in this expanding field of
Bacillus, Enterobacteriaceae, and Lysinibacillus taxa, in the root phytohormone–microbiome interactions for both fundamental
microbiome (Carvalhais et al., 2015). A study in 2007 showed that and applied research.
plants deficient in JA-mediated defenses had greater epiphytic
bacterial diversity (Kniskern et al., 2007).
In addition to JA and SA, ethylene (ET), another Infected Plants Recruit Beneficial
phytohormone, can also diffuse through air- and water- Microbes
filled pores in the soil (Broekgaarden et al., 2015). Similar to SA Interestingly, plants infected by pathogens may change their
and JA, ET can modulate arbuscular mycorrhizal colonization root exudates which may serve as signals to recruit beneficial
and root nodulation in legume-rhizobia symbioses (Nascimento root microbes. For example, upon attack by fluorescent
et al., 2018). Therefore, like many VOCs, ET has a wide effective pseudomonads (P. protegens), Ordeum vulgare L. selectively
range in soil, including mediating long-distance attraction of recruited the Fluorescent pseudomonads carrying antifungal
bacteria to roots. For example, studies on ET mutants showed traits to its root microbiome. Such a recruitment leads to a
that mutations in the ein2 gene altered rhizosphere microbiome reduced impact by the pathogen on host plants (Dudenhöffer
(Doornbos et al., 2011). A recent study also suggested that ET et al., 2016). The same phenomenon was found in citrus root-
production in peanut roots induced by cyanide could alter the associated microbiome change upon infection by Huanglongbing
microbiome and re-assembled the microbial co-occurrence (HLB) (Zhang et al., 2017). In Arabidopsis, plants challenged
network of peanuts by increasing the abundance of Catenulispora by the foliar pathogen Pseudomonas syringae pv. tomato (Pst)
sp., a keystone actinobacterium, in the intercropped peanut exudated lower levels of sugars, alcohols, and short-chain organic
rhizosphere (Chen Y. et al., 2020). While the mechanism of how acids (SCOAs) and higher levels of amino acids, nucleotides,
ET works in mediating the plant microbiome is not known, and long-chain organic acids (LCOAs). These changes lead to
one study suggested that glucosinolate might be involved the recruitment of beneficial rhizosphere microbes, including
(Pangesti et al., 2016). a few in Proteobacteria (Yuan et al., 2018). Similarly, the
infection of sugar beets by the wilt fungal pathogen Rhizoctonia Microbiomes Contribute to Productions
solani caused the enrichment of several endophytic bacteria of PSMs in Medicinal Plants
belonging to Chitinophaga, Flavobacterium, and Pseudomonas
For medicinal plants, investigations have shown that the
species resulting in an activation of their biosynthetic gene
plant microbiomes could influence host plants’ productivity of
clusters to suppress the fungal pathogen (Carrion et al., 2019).
important medicinal components such as alkaloids, steroids,
These organisms produce antifungal effectors, including cell
terpenoids, etc. For example, two recent studies indicated
wall-degrading enzymes, and secondary metabolites such as
that plant–microbiome interactions could improve biomass
phenazines, polyketides, and siderophores, that can contribute to
production of Salvia miltiorrhiza and influence tanshinone
their effects on the root mycobiome.
production, which is the major class of bioactive medicinal
components from this plant (Chen et al., 2018; Huang et al.,
Secreted Root Mucilage Shapes the 2018). In this study, S. miltiorrhiza possesses a distinctive
Nitrogen-Fixation Microbiome seed-associated microbiome, including Pantoea, Pseudomonas,
A study on Mexican maize found that the mucilage associated Sphingomonas, and Dothideomycetes. This microbiome contains
with the aerial roots of Sierra Mixe maize Z. mays ssp. mexicana a gene reservoir related to the synthesis of forterpenoid
(teosinte) can feed a complex diazotrophic microbiome. The backbone and other compounds, thus providing additional
diazotrophic microbiome includes microbes containing active metabolic capabilities to host plants (Chen et al., 2018).
nitrogenase, and the fixed nitrogen can be efficiently transported Another study suggested that Echinacea purpurea is an excellent
from the nitrogen-fixing microbes to host plants (Van Deynze model for studying medicinal plant–microbiome interactions
et al., 2018). Interestingly, this mechanism allows maize to fix (Maggini et al., 2020). The E. purpurea microbiome (bacterial
up to 82% of its nitrogen needs from the atmosphere. The strains isolated from stems and leaves) interaction model
maize mucilage was rich in monosaccharides such as arabinose, showed that microbiome can affect the production of VOCs,
fucose, galactose, xylose, glucuronic acid, and mannose. Unlike phenylpropanoid, and alkamides in the plants (Maggini et al.,
most modern maize varieties, the Sierra Mixe maize variety 2017, 2019a,b).
can develop extensive aerial roots and secrete large amounts of
mucilage after rain (Bennett et al., 2020). The monosaccharides Microbiome Contributes to Functional
in mucilage is not commonly found in plant cell walls and
may select for specific mutualistic, nitrogen-fixing bacteria
PSMs of Economic Crops and Other
that are uniquely capable of degrading and consuming the Plants
mucilage mono- and poly- polysaccharide in exchange for fixing Aside from medicinal plants, other economic crops, such
atmospheric nitrogen to benefit the plants (Amicucci et al., as Cannabis sativa, are attractive host plants to investigate
2019). The study paves the way toward developing innovative plant–microbiome interactions. Cannabis sativa produces
strategies for biological nitrogen fixation in cereal plants. Indeed, many functional secondary metabolites. Recent research
a model for plant-microbe association capable of supporting showed that the endophytic bacteria (plant growth-promoting
diazotrophic activity was proposed to support nitrogen fixation bacteria, PGPR) consortium within C. sativa included
in cereal crops (Bennett et al., 2020). On the other hand, mucilage Azospirillum brasilense, Gluconacetobacter diazotrophicus,
may contain proteins and other metabolites with antimicrobials Burkholderia ambifaria, and Herbaspirillum seropedicae.
that function in defense against fungal and bacterial pathogens These endophytic microbes facilitated the growth and
(Sasse et al., 2018). development of Cannabis and the accumulation of 19-
tetrahydrocannabinol (THC) and cannabidiol (CBD) (Pagnani
et al., 2018; Taghinasab and Jabaji, 2020).
PLANT MICROBIOMES CONTRIBUTE TO Similarly, inoculation of Papaver somniferum L. with a
THE PRODUCTIONS OF PSMs consortium of Marmoricola sp. and Acinetobacter sp. increased
the morphine yield by enhancing the expression of COR, a key
Previous studies have highlighted the capabilities of plant gene for morphine biosynthesis (Ray T. et al., 2019). In addition,
microbiomes to influence important plant traits, such as growth, three fungal endophytes (Fusarium redolens, Phialemoniopsis
abiotic stress tolerance, resistance to infectious diseases, and cornearis, and Macrophomina pseudophaseolina) were found
the synthesis of plant growth promoting (PGP) hormones. At to regulate forskolin biosynthesis in Coleus forskohlii (Mastan
present, our understanding of the effects of the microbiome et al., 2019). Plants can also detect certain molecules released
on PSMs, including their mechanism of action remains quite by microbiomes through a chemical recognition system, which
limited. This is different from the large body of literature can subsequently trigger plants to generate signal transduction
showing how PSMs can shape the plant–microbiome structure. networks and make corresponding changes in related gene
Improved understanding of PSMs profiles could be achieved by activities, and leading to the accumulation of certain PSMs
investigating the interaction of the plant (especially medicinal (Tidke et al., 2019). Importantly, horizontal gene transfer
plants and economic crops) with their microbiomes. According (HGT) in plants-endophytes may also lead to changes in
to a recent study by Finkel et al. (2020), bacteria in the genus plant secondary metabolic products (Wang et al., 2019).
Variovorax manipulated Arabidopsis root growth and host plant One recent study showed that local colonization of roots by
auxin and ethylene levels to influence the development of the bacteria in the genus Bacillus triggered systemic exudation
Arabidopsis root. of acylsugars SMs in tomato (Korenblum et al., 2020). Both
leaf and root metabolomes and transcriptomes changed due in roots and shoots of various crop species (Korenblum and
to differences in the root microbiome community structure, Aharoni, 2019; Ray S. et al., 2019).
with different microbiomes inducing specific changes in tomato
root exudation, a process called the systemically induced
root exudation of PSMs (SIREM) (Korenblum et al., 2020). Microbial Secondary Metabolites (MSMs)
However, the underlying molecular mechanisms of functional Influence Plant Traits
PSMs synthesis regulated by microbiome- have not been While the focus of this review is on how PSMs impact
completely elucidated. plant microbiomes and how the plant microbiomes can
influence the production of PSMs, there have been extensive
Microbiomes Influence Plant VOCs documentations of how microbial secondary metabolites (MSMs)
Plant microbiomes can participate in and/or influence the can impact plant growth and development. Here we describe
production of plant VOCs. For example, the suppression of a few examples. On the one hand, many plant pathogenic
phyllospheric microbiome in Sambucus nigra by antibiotic microbes can secrete toxins that cause diseases and death to
fumigation also changed the composition and proportion of plants. For example, sphinganine-analog mycotoxins including
terpenes in the volatile mix (Peñuelas et al., 2014). This result fumonisins and AAL-toxins produced by plant pathogenic
was confirmed in a later research showing that the application of fungi in the Fusarium genus and in Alternaria alternata
antibiotics decreased the concentration of acetyl-CoA, citraconic f. sp. Lycopersici respectively have diverse cytotoxicity and
acid, isoleucine, and several other PSMs (such as terpenes and phytotoxicity and are a destructive force to crop production
phenols in the epiphytic extracts) in the same plant S. nigra worldwide (Chen J. et al., 2020). On the other hand, there
(Gargallo-Garriga et al., 2016). Similar observations were made are many examples of bacteria and fungi that produce
in Penstemon digitalis (Burdon et al., 2018), Arabidopsis thaliana plant growth – promoting SMs. For example, rhizobacterium
(Raza et al., 2020), Brassica rapa (Helletsgruber et al., 2017), Bacillus tequilensis SSB07 produces several phytohormones
petunia (Boachon et al., 2019b), and Atractylodes lancea (Zhou including gibberellins (GA1, GA3, GA5, GA8, GA19, GA24,
et al., 2018). A recent review provided an excellent summary and GA53), indole-3-acetic acid, and ABA. Application of
on the effects of plant microbiomes on plant VOC emissions B. tequilensis SSB07 enhanced the growth of Chinese cabbage
(Schenkel et al., 2019). seedlings and increased the shoot length and biomass, leaf
development, and photosynthetic pigment contents of soybeans.
For B. tequilensis SSB07, its plant growth-enhancing effects were
Are Secondary Metabolites From Plants further increased under heat stress, by significantly upregulating
or Their Microbiomes? the endogenous JA and SA contents in the soybean phyllosphere
The subsections above discussed how the plant microbiome while down-regulating the production of stress-responsive ABA
could contribute to host PSMs. However, it is entirely (Kang et al., 2019).
possible that some of these so-called “PSMs” could be the The positive effects of MSMs on plant growths are shown
biosynthetic products of their plant microbiome, including not only for agricultural crops and vegetables but also for
those by their endophytic microbes. Endophytes can produce trees. For example, two bacterial strains, Bacillus sp. s50 and
diverse classes of phytochemicals, including podophyllotoxin, Paenibacillus sp. s37, recently showed significant effects on Abies
paclitaxel (taxol), deoxypodophyllotoxin, and camptothecin nordmanniana, the most common Christmas tree species in
that are also produced by plants (Etalo et al., 2018b; the world. Both bacteria produced high quantities of indole-3-
Furtado et al., 2019; Mastan et al., 2019). A previous review acetic acid, with Bacillus sp. s50 increased the seed germination
discussed endophytic microbiome as potential sources of rate and systemic resistance to pathogens while Paenibacillus sp.
bioactive compounds (Ray S. et al., 2019). It is necessary s37 increased plant root growth in both greenhouse and field
to distinguish which of these compounds are produced conditions (Garcia-Lemos et al., 2020). Similar to those found
by host plants and which ones by the plant microbiome. in PGP rhizobacteria, several fungal species such as Trichoderma
Such knowledge will help with novel developments in the virens are also known to produce indole-3-acetic acid and other
in situ analysis of metabolites during the interaction between auxin-related compounds to positively impact the growth and
plants and microbes. development of plants, including rice, cotton, and Arabidopsis
Aside from produce secondary metabolites similar to those (Contreras-Cornejo et al., 2009).
produced by plants, endophytes can metabolize secondary Aside from phytohormones, the plant microbiomes can also
compounds produced by host plants. For example, the produce abundant VOCs that can impact plant phenotypes
leaf endophytic mycobiome could metabolize glycosylated (Kai et al., 2009). Many VOCs have been reported from the
flavonoids, the secondary metabolome of Cephalotaxus plant microbiome, including alcohols, aldehydes, ammonia,
harringtonia (Tian et al., 2014). In another example, acids, ketones, esters, and terpenes. These microbial VOCs
deglycosylated flavonoids showed beneficial effects on the can influence plant communications, participate in defense
hyphal growth of their endophytic fungi. Similarly, the against pathogens, and promote plant growth and development
biotransformation of Huperzine has also been found in fungal (Ortíz-Castro et al., 2009). For example, VOCs emitted by
endophytes of Huperzia serrata (Zhan et al., 2019). Two recent the Bacillus subtilis GB03 can trigger changes in major
reviews summarized microbiome-induced metabolic changes hormonal signaling networks in A. thaliana and impact
the expressions of over 600 genes related to cell wall of humus in soil (Sokol et al., 2019). Such studies suggest
modifications, primary and secondary metabolisms, stress that PSMs may be central to ecosystem responses to abiotic
responses and auxin homeostasis (Zhang et al., 2007). The stresses and that we need an integrated approach to enhance
VOCs emitted by strain B. subtilis GB03 included short- the joint plant-microbiome responses to stresses. On the one
chained alcohols, aldehydes, acids, esters, ketones, hydrocarbons, hand, PSMs through root exudates can be abiotic stress response
and sulfur-containing compounds and these VOCs increased mediators. For example, changes in root exudates can help
photosynthetic efficiency and chlorophyll content in A. thaliana. recruit microbiome associations to improve nutrient and water
Overall, many microbial VOCs analyzed so far showed evidence retentions (Huang et al., 2017), and to reduce damaging
of not only impacting plants directly but also indirectly reactive oxygen species (ROS) by increasing the production
such as by regulating the activities of herbivorous insects of root peroxidases (Naylor and Coleman-Derr, 2017). The
and plant parasitic nematodes (Hansen and Moran, 2014; exudates of Quercus ilex under drought stress contained
Zhang et al., 2020). primarily SMs (71% of total metabolites) (Gargallo-Garriga
et al., 2018), brought about mainly by regulating the expression
of genes involved in secondary metabolite biosynthesis (Xu
et al., 2018; Varoquaux et al., 2019). The altered PSMs
PSMs–MICROBIOME INTERACTIONS further influence the structure of root microbiome, including
IMPACT CROP BREEDING, ABIOTIC the recruitment of Actinobacteria, Streptomyces or Firmicutes,
STRESS RESPONSE, AND PLANT contributing to the plants’ DefenseBiome and enhancing
INVASION the plants’ survival under conditions (Bakker P. A. H. M.
et al., 2018; Liu and Brettell, 2019; Liu H. et al., 2020;
Plant hosts and their microbiome are highly interlinked and may Williams and de Vries, 2020). Together, these studies suggested
have co-evolved to function as a meta-organism or holobiont that root exudates could serve as signals to reshape root
with integrated ecologies. In domesticated crops (predominantly microbiome, by acting as chemoattractant or nutrition sources
selected for yield traits), microbiomes can also be domesticated, to reconstruct microbiomes to help alleviate abiotic stresses
causing different cultivars to be preferentially associated with on host plants. At present, the exact chemicals that promote
different microbiomes (Escudero-Martinez and Bulgarelli, 2019). such relationships remain largely unknown. Deciphering this
A number of studies suggested that crop microbiomes may have interaction could advance our ability to use microbiome to
been affected by the domestication process in several crops, enhance abiotic stress tolerance in crop plants (Cheng et al., 2019;
including barley (Bulgarelli et al., 2015), rice (Edwards et al., de Vries et al., 2020).
2018), and the common bean (Perez-Jaramillo et al., 2019). Invasive plants can change element cycling, soil nutrient
These studies revealed the differences in plant microbiomes pools, and/or soil microbiome that can all potentially accelerate
between modern cultivars and their wild ancestors in these further invasion and prevent re-establishment of native species
species. Further studies identified that domestication changed (Stefanowicz et al., 2017). An example is the invasive plant
root exudates and several secondary metabolites in modern Ageratina adenophora that changed the local soil microbial
varieties, likely contributing to the recruitment and maintenance community and further enhanced A. adenophora’s competitive
of the plant microbiomes (Iannucci et al., 2017). The findings on advantage over native plants (Chen L. et al., 2019). The detection
PSMs–microbiome interactions have provided valuable insights and allelopathy of plant neighbors are driven by signal chemicals
to guide microbiome-based approaches to improve agricultural secreted by roots. There have been many studies on the role
productivity. Given the large species diversity and enormous of below-ground function of PSMs-microbiome, such as plants
number of potential interactions between PSMs and microbes releasing SMs (also including VOCs) to communicate with
within individual plants, we are far from understanding the their root microbiome to gain a competitive advantage over
biology of the plant system and its microbiome (or PSMs and other plants (Schandry and Becker, 2020). An example of PSM
microbiome). Identifying specific variations in root exudation attracting beneficial microbes was shown in maize with exudate
among plant species and genotypes could suggest the potential Benzoxazinoids attracting plant-beneficial Pseudomonas strains
for manipulation of root exudation or PSMs in agricultural to the maize rhizosphere (Ahmad et al., 2011; Cotton et al., 2019).
cultivars, in order to create specific selective effects on the plant Another study supported a scenario in which an invasive plant,
microbiome (Bakker et al., 2012). the Chinese tallow tree (Triadica sebifera), enhanced its AMF
Despite many studies on abiotic stress tolerance of crop association and invasion success by changing its root flavonoid
species, responses of roots to such stresses have so far largely metabolism (Pei et al., 2020). Similar findings have been reported
been overlooked. A recent review indicated that plant-associated from thistle (Verbeek and Kotanen, 2019), Spartina alterniflora
microbiomes can influence several plant traits including growth (Yang et al., 2019), and others (Kamutando et al., 2019; Pei et al.,
and abiotic stress tolerance (de Vries et al., 2020). Similarly, 2020). The recruited microbiome of invasive plants could directly
host plants also can adapt to changing environments by or indirectly interfere their antagonism toward other plants via
adjusting their production of PSMs (Bont et al., 2020). Indeed, SMs, enhancing host plant nutrient acquisition (phosphorous
interests in PSMs have been significantly enhanced with the and nitrogen) and modulating host root physiology (such as root
knowledge of its importance in enhancing abiotic stress tolerance exudation). Many crop species (including wheat, maize, and rice)
(de Vries et al., 2020), plant nutrient uptake, and the formation are allelopathic, thus, targeted exploitation of allelopathy among
plants to reduce weed invasion coupled with a simultaneous Methods for Detecting and Tracking
reduction of herbicide application provides an attractive option Plant Secondary Metabolites
for sustainable agriculture (Schandry and Becker, 2020). For
The focus of this review is on the interaction between
example, investigating model SynComs with various PSMs-
PSMs–microbiome. Thus, it’s important to discuss methods
microbiome strategies can help derive methods to suppress
for plant metabolome analysis. Metabolome analyses include
parasitic weeds in agricultural field. Such methods hold great
data acquisition and processing. Data processing includes data
promise for developing novel integrated crop management
normalization, peak alignment, and data scaling (Duan and Qi,
strategies (Masteling et al., 2019). However, although some
2015; Tahir et al., 2019). Several excellent software and websites
PSMs such as several VOCs are among the biochemically
are currently available for the processing of NMR and MS data.
best-characterized allelochemicals, the extent and the molecular
These include MZmine 2, XCMS, Open MS, Decon2LS, and MS-
mechanisms by which the release of PSMs influencing the root
DIAL, all of which have been extensively used for diverse sets of
microbiome requires further investigation.
metabolomics data. Misra (2020) provided a recent review that
Phosphate is a limiting nutrient in most crop fields. However,
summarized over 95 metabolomics tools, software, and database.
the effects of phosphate on microbiome have not been fully
In addition, the fine-scale dynamics between the PSMs-
described. At present, there are two opposing types of results.
microbiome are of special importance to improve our
In the first, microbes recruited by the PSMs under phosphate
understanding on plant–microbe interactions. Indeed, there
limitation provide the plants an advantage in coping with
is a growing interest in tracing and narrowing PSMs analyses
phosphate limitation (Castrillo et al., 2017; Fabiańska et al.,
down to single-cell level, which will be helpful to observe
2019; You et al., 2020). On the other hand, the microbes could
in-situ metabolism and trace metabolites in plant–microbiome
extract the limited amount of phosphate from the soil and
interaction. Sensitive detection technologies and innovative cell-
make the phosphate less available to plants (Finkel et al., 2019).
sampling techniques are needed to profile and trace metabolites
Together, these results suggest that different plant-microbiome
in single cells. However, the field is still in its infancy for
combinations likely react to phosphate limitations differently.
plant research. As PSMs are accumulated due to the activities
Further research is needed to understand how PSMs might be
of both host plant and its microbiome, strategies that allow
involved in mediating the plant–microbiome interactions for
metabolite traceability should be used to elucidate the origin
individual species during phosphate starvation.
of metabolites and to interpret their actions. The studies of
the intestinal microbiome from humans and animals provide
good references from which to design similar studies on plant–
DISCUSSION AND FUTURE PROSPECTS microbiome interactions (Koh et al., 2018; Duncan et al., 2019;
Nemet et al., 2020).
While studies on the human (gut) microbiome have stolen
One approach called Exometabolomics could provide novel
most of the limelight, botanists have also been making progress
insights into root microbiome. This approach investigates
toward elucidating the composition and function of plant
the root-derived compounds as carbon sources consumed by
microbiomes and PSMs over the last few years. In spite of a
individual microbial strains and identifies substrate preferences
large number of contributions on plant microbiome, a thorough
of individual microbes from a mixture of exuded metabolites
comprehension on plant microbiome structure, dynamics, and
(Jacoby et al., 2018). Unfortunately, tracking the dynamics
function associated with PSMs still remains largely unexplored.
of root–microbiome interactions at high spatial resolution is
One potential area of research involves understanding the
still time consuming and requires significant expertise. Other
factors influencing plant microbiome assembly, and the signaling
methods include a microfluidics-based approach termed tracking
crosstalk in plant–microbiome interactions (Sasse et al., 2018).
root interactions system (TRIS) (Massalha et al., 2017) and a root-
On the one hand, systematic research on the associated
microbe interaction chip (RMI-Chip) (Noirot-Gros et al., 2020).
microbiomes in model plants, such as Arabidopsis, rice and
These biosensors (Pini et al., 2017) or microfluidics (Millet et al.,
maize, could help clarify the roles microbes may play in
2019) based methods enable direct imaging of root–microbiome
modulating the biosynthetic pathways of PSMs. Approaches
interactions in real time, and provide spatiotemporal non-
such as SynCom may provide both functional and mechanistic
destructive analysis of samples in situ (Lenzewski et al., 2018). On
insights into how plants regulate their microbiomes, and on
the other hand, methods for whole-sample metabolic profiling
how the microbiomes influence PSMs. Secondly, the single-
of non-sterile rhizosphere soil have also been explored (Petriacq
cell genomics and specialized plant metabolome analytical
et al., 2017). These novel approaches thus allow researchers
tools are opening new possibilities for a diversity of potential
to investigate microbiome substrate preference for a number
research topics. Thirdly, spatial patterns of PSMs–microbiome
of metabolites at the same time, mimicking the real PSMs–
interactions are largely unexplored. To improve the root exudate
microbiome interactions.
analysis, several modern technologies such as microfluidics and
bacterial biosensors that respond to selected PSMs have been
introduced (Massalha et al., 2017). And last but not the least, Bioinformatics of Plant
the underpinning genetic controls on PSMs and how they are Metabolome–Microbiome Interactions
affected by changing microbiomes and environmental conditions Aside from the development in hardware for data acquisition,
require greater focus. software that integrates information from both the metabolome
and the microbiome is also needed. For example, statistical microbiome membership and host plant phenotypes, potentially
methods for metabolome-microbiome data integration have been allowing the design of novel communities (Herrera Paredes et al.,
developed to identify the potential molecular markers driving 2018). In addition, SynComs can be further combined with
their interactions (Lamichhane et al., 2018). Unfortunately, PSMs detection technologies. In summary, SynCom systems can
though improvements have been made, complete annotation of provide crucial insights into the two-way interactions between
plant metabolomes is not yet possible (Lucaciu et al., 2019). PSMs and plant microbiome.
Furthermore, there is a lack of in-depth understanding on how to
integrate multi-omics data such as those from the proteome and Connecting PSMs–Microbiome
transcriptome. The development of more reliable bioinformatics Relationships With Plant Breeding
tools such as neural networks method is also urgent. Plant scientists are beginning to consider the plant microbiome
Despite these potential problems, recent studies suggested that as plants’ “secondary genome” that can provide host plants with
untargeted metabolomics datasets showed a closer correlation microbe-derived metabolites and traits. During traditional crop
with the microbiome data than those of targeted approaches, breeding, breeders select traits for yield or nutrition but not
especially when they are compared with specific microbial for PSMs-microbiome relationships. However, as shown above,
metabolites (Melnik et al., 2017; Lamichhane et al., 2018). At microbiomes can respond rapidly to changes in PSMs such as
present, several metabolite analysis methods are available and those in root exudates and in the phyllosphere. Consequently,
their use depends mainly on study objectives. These metabolic the plant microbiome could be treated as a selectable trait during
profiling methods include nontargeted metabolomics, widely breeding that could be manipulated chemically through PSMs.
targeted metabolites, metabolite target analysis (targeted), and A pre-requisite for success in such a breeding program is a
metabolite fingerprinting (Tahir et al., 2019). A new integrated broad understanding of the relationships and changes of PSMs
method named ESI-triple quadrupole-linear ion trap (Q TRAP)- and microbiome during crop domestication. As described above,
MS (Luo et al., 2016) or ESI-QqTOF-MS (Chen et al., 2013) domestication can modify PSMs – microbiome relationship.
for large-scale detection, identification, and quantification of Furthermore, previous studies have shown that different corps
common metabolites has also been developed (Duncan et al., attract different microbiomes and that the microbiomes can
2019; Kozuka et al., 2020). However, there is no specialized have different effects on different host plants. A recent review
database for plant microbiome–metabolome information that is proposed using desirable microbiomes as selective markers to
linked to environmental conditions (Lucaciu et al., 2019). Priority identify potential beneficial microbiome for specific crop varieties
needs to be given to the development of such databases for (Pascale et al., 2020). In this proposal, PSMs play a key role in the
functional interpretation of the increasingly common large-scale selection process, by attracting various beneficial microbes and/or
multi-omics plant microbiome data. repelling detrimental one.
At present, in-depth and systematic investigations on the
Confirming Causal Relationship Between effects of the PSMs and functional microbiome on economic
PSMs–Microbiome Interactions Using crops are relatively limited. Indeed, the function and dynamics
of PSMs-functional microbiome interactions remain unexplored
Synthetic Communities in most economic crops. Some economic crops, such as garlic and
Both the plant microbiome and PSMs play important roles in ginger, can be widely used as models to analyze such interactions
plant health, impacting agriculture and food security (Haney and to enhance the production of the desirable metabolites
et al., 2015). Though progresses have been made in our such as allicin and curcumin for commercial purposes. Indeed,
understanding of their interactions, many questions remain. For understanding the relationship between economic crop PSMs
example, which special microbiome was attracted by PSMs and and functional microbiome can lead to improved agricultural
how to maintain the activities and abundance of PSMs? How practices that enhance plant fitness and increase the yield of
do PSMs discriminate beneficial microbiome from pathogenic functional secondary metabolites.
ones? Future research efforts should be devoted to understanding
the modes with which microbiome affects PSMs in various
plant tissues, evaluating the direction and magnitude of changes AUTHOR CONTRIBUTIONS
in microbiome as mediated by PSMs. Similarly, understanding
how changes in PSMs are affected by the plant microbiomes is YC and JX conceived, structured, and finalized the manuscript.
also important. A promising approach to understand reciprocal ZP coordinated the literature research and drafted the initial
effects of plants and their microbiota is through SynCom, version of the manuscript. All authors contributed to the
using sequenced and cultivated bacteria to provide simple and literature search and reviewing and finalizing the manuscript.
reproducible systems to study PSMs–microbiome interactions
(Durán et al., 2018; Liu et al., 2019). Such a system allows
precise variations in stress levels, exposure to infectious agents, FUNDING
phytohormone concentrations and metabolism, nutrition supply,
etc. (Koprivova et al., 2019; Liu H. et al., 2020). Another study This work was financially supported by scholarships and grants
developed a machine learning computational approach to design from the Agricultural Science and Technology Innovation
SynCom, making it possible to infer causal relationships between Program of the Chinese Academy of Agricultural Sciences
(CAAS-ASTIP-2015-IBFC), the Elite Youth program of the 531998 and CRDPJ 474638-14) of Canada, and the Fundamental
Chinese Academy of Agricultural Sciences, the Natural Sciences Research Funds for the Central Public-interest Scientific
and Engineering Research Council (NSERC Discovery Grant Institution (1610242020007).
REFERENCES Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D.,
Costello, E. K., et al. (2010). Qiime allows analysis of high-throughput
Ahmad, S., Veyrat, N., Gordon-Weeks, R., Zhang, Y., Martin, J., Smart, L., et al. community sequencing data. Nat. Methods 7, 335–336. doi: 10.1038/nmeth.f.
(2011). Benzoxazinoid metabolites regulate innate immunity against aphids and 303
fungi in maize. Plant Physiol. 157, 317–327. doi: 10.1104/pp.111.180224 Carrion, V. J., Perez-Jaramillo, J., Cordovez, V., Tracanna, V., de Hollander, M.,
Amicucci, M. J., Galermo, A. G., Guerrero, A., Treves, G., Nandita, E., Kailemia, Ruiz-Buck, D., et al. (2019). Pathogen-induced activation of disease-suppressive
M. J., et al. (2019). Strategy for structural elucidation of polysaccharides: functions in the endophytic root microbiome. Science 366, 606–612. doi: 10.
elucidation of a maize mucilage that harbors diazotrophic bacteria. Anal. Chem. 1126/science.aaw9285
91, 7254–7265. doi: 10.1021/acs.analchem.9b00789 Carvalhais, L. C., Dennis, P. G., Badri, D. V., Kidd, B. N., Vivanco, J. M., and
Bakker, M. G., Manter, D. K., Sheflin, A. M., Weir, T. L., and Vivanco, J. M. Schenk, P. M. (2015). Linking jasmonic acid signaling, root exudates, and
(2012). Harnessing the rhizosphere microbiome through plant breeding and rhizosphere microbiomes. Mol. Plant Microbe Interact. 28, 1049–1058. doi:
agricultural management. Plant Soil. 360, 1–13. doi: 10.1007/s11104-012- 10.1094/MPMI-01-15-0016-R
1361-x Carvalhais, L. C., Dennis, P. G., Badri, D. V., Tyson, G. W., Vivanco, J. M.,
Bakker, O. B., Aguirre-Gamboa, R., Sanna, S., Oosting, M., Smeekens, S. P., Jaeger, and Schenk, P. M. (2013). Activation of the jasmonic acid plant defence
M., et al. (2018). Integration of multi-omics data and deep phenotyping enables pathway alters the composition of rhizosphere bacterial communities. PLoS One
prediction of cytokine responses. Nat. Immunol. 19, 776–786. doi: 10.1038/ 8:e56457. doi: 10.1371/journal.pone.0056457
s41590-018-0121-3 Carvalhais, L. C., Dennis, P. G., and Schenk, P. M. (2014). Plant defence inducers
Bakker, P. A. H. M., Pieterse, C. M. J., de Jonge, R., and Berendsen, R. L. (2018). rapidly influence the diversity of bacterial communities in a potting mix. Appl.
The soil-borne legacy. Cell 172, 1178–1180. doi: 10.1016/j.cell.2018.02.024 Soil Ecol. 84, 1–5. doi: 10.1016/j.apsoil.2014.06.011
Battin, T. J., Besemer, K., Bengtsson, M. M., Romani, A. M., and Packmann, Carvalhais, L. C., Schenk, P. M., and Dennis, P. G. (2017). Jasmonic acid signalling
A. I. (2016). The ecology and biogeochemistry of stream biofilms. Nat. Rev. and the plant holobiont. Curr. Opin. Microbiol. 37, 42–47. doi: 10.1016/j.mib.
Microbiol. 14, 251–263. doi: 10.1038/nrmicro.2016.15 2017.03.009
Bennett, A. B., Pankievicz, V. C. S., and Ane, J. M. (2020). A model for nitrogen Castrillo, G., Teixeira, P. J., Paredes, S. H., Law, T. F., de Lorenzo, L., Feltcher, M. E.,
fixation in cereal crops. Trends Plant Sci. 25, 226–235. doi: 10.1016/j.tplants. et al. (2017). Root microbiota drive direct integration of phosphate stress and
2019.12.004 immunity. Nature 543, 513–518. doi: 10.1038/nature21417
Bhattacharjee, A., Velickovic, D., Wietsma, T. W., Bell, S. L., Jansson, J. K., Chen, H., Wu, H., Yan, B., Zhao, H., Liu, F., Zhang, H., et al. (2018). Core
Hofmockel, K. S., et al. (2020). Visualizing microbial community dynamics via microbiome of medicinal plant salvia miltiorrhiza seed: a rich reservoir of
a controllable soil environment. Msystems 5:e645-19. doi: 10.1128/mSystems. beneficial microbes for secondary metabolism? Int. J. Mol. Sci. 19:672. doi:
00645-19 10.3390/ijms19030672
Boachon, B., Burdloff, Y., Ruan, J.-X., Rojo, R., Junker, R. R., Vincent, B., et al. Chen, J., Li, Z. M., Cheng, Y., Gao, C. S., Guo, L. T., Wang, T. H., et al. (2020).
(2019a). A promiscuous cyp706a3 reduces terpene volatile emission from Sphinganine-analog mycotoxins (SAMs): chemical structures, bioactivities, and
Arabidopsis flowers, affecting florivores and the floral microbiome. Plant Cell genetic controls. J. Fungi. 6:312. doi: 10.3390/jof6040312
31, 2947–2972. doi: 10.1105/tpc.19.00320 Chen, L., Fang, K., Zhou, J., Yang, Z. P., Dong, X. F., Dai, G. H., et al.
Boachon, B., Lynch, J. H., Ray, S., Yuan, J., Caldo, K. M. P., Junker, R. R., et al. (2019). Enrichment of soil rare bacteria in root by an invasive plant ageratina
(2019b). Natural fumigation as a mechanism for volatile transport between adenophora. Sci. Total Environ. 683, 202–209. doi: 10.1016/j.scitotenv.2019.05.
flower organs. Nat. Chem. Biol. 15, 583–588. doi: 10.1038/s41589-019-0287-5 220
Bodenhausen, N., Bortfeld-Miller, M., Ackermann, M., and Vorholt, J. A. Chen, M. X., Wang, S. Y., Kuo, C. H., and Tsai, I. L. (2019). Metabolome
(2014). A synthetic community approach reveals plant genotypes affecting the analysis for investigating host-gut microbiota interactions. J. Formos. Med.
phyllosphere microbiota. PLoS Genet. 10:e1004283. doi: 10.1371/journal.pgen. Assoc. 118(Suppl. 1), S10–S22. doi: 10.1016/j.jfma.2018.09.007
1004283 Chen, Q., Jiang, T., Liu, Y. X., Liu, H., Zhao, T., Liu, Z., et al. (2019). Recently
Bont, Z., Züst, T., Arce, C. C. M., Huber, M., and Erb, M. (2020). Heritable variation duplicated sesterterpene (c25) gene clusters in Arabidopsis thaliana modulate
in root secondary metabolites is associated with recent climate. J. Ecol. 108, root microbiota. Sci. China Life Sci. 62, 947–958. doi: 10.1007/s11427-019-
2611–2624. doi: 10.1111/1365-2745.13441 9521-2
Boughton, B. A., and Thinagaran, D. (2018). “Mass spectrometry imaging (msi) Chen, Q.-L., Hu, H.-W., Zhu, D., Ding, J., Yan, Z.-Z., He, J.-Z., et al. (2020). Host
for plant metabolomics,” in Plant Metabolomics: Methods and Protocols, ed. C. identity determines plant associated resistomes. Environ. Pollut. 258:113709.
António (New York, NY: Springer). doi: 10.1016/j.envpol.2019.113709
Brader, G., Compant, S., Mitter, B., Trognitz, F., and Sessitsch, A. (2014). Metabolic Chen, W., Gong, L., Guo, Z., Wang, W., Zhang, H., Liu, X., et al.
potential of endophytic bacteria. Curr. Opin. Biotechnol. 27, 30–37. doi: 10. (2013). A novel integrated method for large-scale detection, identification,
1016/j.copbio.2013.09.012 and quantification of widely targeted metabolites: application in the
Broekgaarden, C., Caarls, L., Vos, I. A., Pieterse, C. M., and Van Wees, S. C. (2015). study of rice metabolomics. Mol. Plant. 6, 1769–1780. doi: 10.1093/mp/
Ethylene: traffic controller on hormonal crossroads to defense. Plant Physiol. sst080
169, 2371–2379. doi: 10.1104/pp.15.01020 Chen, X., Marszałkowska, M., and Reinhold-Hurek, B. (2020). Jasmonic acid, not
Bulgarelli, D., Garrido-Oter, R., Münch, Philipp, C., Weiman, A., Dröge, J., et al. salicyclic acid restricts endophytic root colonization of rice. Front. Plant Sci.
(2015). Structure and function of the bacterial root microbiota in wild and 10:1758. doi: 10.3389/fpls.2019.01758
domesticated barley. Cell Host Microbe. 17, 392–403. doi: 10.1016/j.chom.2015. Chen, Y., Bonkowski, M., Shen, Y., Griffiths, B. S., Jiang, Y., Wang, X., et al. (2020).
01.011 Root ethylene mediates rhizosphere microbial community reconstruction when
Burdon, R. C. F., Junker, R. R., Scofield, D. G., and Parachnowitsch, A. L. chemically detecting cyanide produced by neighbouring plants. Microbiome 8:4.
(2018). Bacteria colonising penstemon digitalis show volatile and tissue-specific doi: 10.1186/s40168-019-0775-6
responses to a natural concentration range of the floral volatile linalool. Cheng, Y. T., Zhang, L., and He, S. Y. (2019). Plant-microbe interactions facing
Chemoecology 28, 11–19. doi: 10.1007/s00049-018-0252-x environmental challenge. Cell Host Microbe. 26, 183–192. doi: 10.1016/j.chom.
Buza, T. M., Tonui, T., Stomeo, F., Tiambo, C., Katani, R., Schilling, M., et al. 2019.07.009
(2019). Imap: an integrated bioinformatics and visualization pipeline for Comeau, A. M., Douglas, G. M., and Langille, M. G. I. (2017). Microbiome
microbiome data analysis. BMC Bioinformatics 20:374. doi: 10.1186/s12859- helper: a custom and streamlined workflow for microbiome research. mSystems
019-2965-4 2:e127-16. doi: 10.1128/mSystems.00127-16
Compant, S., Samad, A., Faist, H., and Sessitsch, A. (2019). A review on the plant Fang, C., Fernie, A. R., and Luo, J. (2019). Exploring the diversity of plant
microbiome: ecology, functions, and emerging trends in microbial application. metabolism. Trends Plant Sci. 24, 83–98. doi: 10.1016/j.tplants.2018.09.006
J. Adv. Res. 19, 29–37. doi: 10.1016/j.jare.2019.03.004 Fang, H., Huang, C., Zhao, H., and Deng, M. (2015). Cclasso: correlation inference
Contreras-Cornejo, H. A., Maciìas-Rodrìguez, L. I., Cortés-Penagos, C., and for compositional data through lasso. Bioinformatics 31, 3172–3180. doi: 10.
Loìpez-Bucio, J. (2009). Trichoderma virens, a plant beneficial fungus, enhances 1093/bioinformatics/btv349
biomass production and promotes lateral root growth through an auxin- Farré-Armengol, G., Filella, I., Llusia, J., and Peñuelas, J. (2016). Bidirectional
dependent mechanism in Arabidopsis. Plant Physiol. 149, 1579–1592. doi: 10. interaction between phyllospheric microbiotas and plant volatile emissions.
1104/pp.108.130369 Trends Plant Sci. 21, 854–860. doi: 10.1016/j.tplants.2016.06.005
Cotton, T. E. A., Petriacq, P., Cameron, D. D., Meselmani, M. A., Schwarzenbacher, Faust, K., Sathirapongsasuti, J. F., Izard, J., Segata, N., Gevers, D., Raes, J., et al.
R., Rolfe, S. A., et al. (2019). Metabolic regulation of the maize rhizobiome by (2012). Microbial co-occurrence relationships in the human microbiome. PLoS
benzoxazinoids. ISME J. 13, 1647–1658. doi: 10.1038/s41396-019-0375-2 Comput. Biol. 8:e1002606. doi: 10.1371/journal.pcbi.1002606
Davis, N. M., Proctor, D. M., Holmes, S. P., Relman, D. A., and Callahan, B. J. Finkel, O. M., Salas-González, I., Castrillo, G., Conway, J. M., Law, T. F., Teixeira,
(2018). Simple statistical identification and removal of contaminant sequences P. J. P. L., et al. (2020). A single bacterial genus maintains root growth in a
in marker-gene and metagenomics data. Microbiome 6:226. doi: 10.1186/ complex microbiome. Nature 587, 103–108. doi: 10.1038/s41586-020-2778-7
s40168-018-0605-2 Finkel, O. M., Salas-González, I., Castrillo, G., Spaepen, S., Law, T. F., Teixeira,
de Vries, F. T., Griffiths, R. I., Knight, C. G., Nicolitch, O., and Williams, A. (2020). P. J. P. L., et al. (2019). The effects of soil phosphorus content on plant
Harnessing rhizosphere microbiomes for drought-resilient crop production. microbiota are driven by the plant phosphate starvation response. PLoS Biol.
Science 368:270. doi: 10.1126/science.aaz5192 17:e3000534. doi: 10.1371/journal.pbio.3000534
Dhariwal, A., Chong, J., Habib, S., King, I. L., Agellon, L. B., and Xia, J. (2017). Friedman, J., and Alm, E. J. (2012). Inferring correlation networks from genomic
Microbiomeanalyst: a web-based tool for comprehensive statistical, visual and survey data. PLoS Comput. Biol. 8:e1002687. doi: 10.1371/journal.pcbi.1002687
meta-analysis of microbiome data. Nucleic Acids Res. 45, W180–W188. doi: Furtado, B. U., Golebiewski, M., Skorupa, M., Hulisz, P., and Hrynkiewicz, K.
10.1093/nar/gkx295 (2019). Bacterial and fungal endophytic microbiomes of salicornia europaea.
Doornbos, R. F., Geraats, B. P., Kuramae, E. E., Van Loon, L. C., and Bakker, P. A. Appl. Environ. Microbiol. 85:e305-19. doi: 10.1128/AEM.00305-19
(2011). Effects of jasmonic acid, ethylene, and salicylic acid signaling on the Garcia, K., Delaux, P. M., Cope, K. R., and Ane, J. M. (2015). Molecular signals
rhizosphere bacterial community of Arabidopsis thaliana. Mol. Plant Microbe required for the establishment and maintenance of ectomycorrhizal symbioses.
Interact. 24, 395–407. doi: 10.1094/mpmi-05-10-0115 New Phytol. 208, 79–87. doi: 10.1111/nph.13423
Duan, L.-X., and Qi, X. (2015). “Metabolite qualitative methods and the Garcia-Lemos, A. M., Großkinsky, D. K., Saleem, A. S., Nicolaisen, M. H., Roitsch,
introduction of metabolomics database,” in Plant metabolomics: Methods and T., Nybroe, O., et al. (2020). Identification of root-associated bacteria that
applications, eds X. Qi, X. Chen, and Y. Wang (Dordrecht: Springer). influence plant physiology, increase seed germination, or promote growth of
Dubey, O., Dubey, S., Schnee, S., Glauser, G., Nawrath, C., Gindro, K., et al. (2020). the christmas tree species Abies nordmanniana. Front. Microbiol. 11:566613.
Plant surface metabolites as potent antifungal agents. Plant Physiol. Biochem. doi: 10.3389/fmicb.2020.566613)
150, 39–48. doi: 10.1016/j.plaphy.2020.02.026 Gargallo-Garriga, A., Preece, C., Sardans, J., Oravec, M., Urban, O., and Peñuelas,
Dudenhöffer, J.-H., Scheu, S., and Jousset, A. (2016). Systemic enrichment of J. (2018). Root exudate metabolomes change under drought and show limited
antifungal traits in the rhizosphere microbiome after pathogen attack. J. Ecol. capacity for recovery. Sci. Rep. 8:12696. doi: 10.1038/s41598-018-30150-0
104, 1566–1575. doi: 10.1111/1365-2745.12626 Gargallo-Garriga, A., Sardans, J., Pérez-Trujillo, M., Guenther, A., Llusià, J., Rico,
Duncan, K. D., Fyrestam, J., and Lanekoff, I. (2019). Advances in mass L., et al. (2016). Shifts in plant foliar and floral metabolomes in response to the
spectrometry based single-cell metabolomics. Analyst 144, 782–793. doi: 10. suppression of the associated microbiota. BMC Plant Biol. 16:78. doi: 10.1186/
1039/c8an01581c s12870-016-0767-7
Durán, P., Thiergart, T., Garrido-Oter, R., Agler, M., Kemen, E., Schulze- Geier, B., Sogin, E. M., Michellod, D., Janda, M., Kompauer, M., Spengler, B.,
Lefert, P., et al. (2018). Microbial interkingdom interactions in roots promote et al. (2020). Spatial metabolomics of in situ host–microbe interactions at the
Arabidopsis survival. Cell 175, 973.e14–983.e14. doi: 10.1016/j.cell.2018.10. micrometre scale. Nat. Microbiol. 5, 498–510. doi: 10.1038/s41564-019-0664-6
020 Gevers, D., Kugathasan, S., Denson, L. A., Vazquez-Baeza, Y., Van Treuren, W.,
Edgar, R. C. (2013). Uparse: highly accurate otu sequences from microbial Ren, B., et al. (2014). The treatment-naive microbiome in new-onset crohn’s
amplicon reads. Nat. Methods 10, 996–998. doi: 10.1038/nmeth.2604 disease. Cell Host Microbe. 15, 382–392. doi: 10.1016/j.chom.2014.02.005
Edgar, R. C., and Flyvbjerg, H. (2015). Error filtering, pair assembly and error Górniak, I., Bartoszewski, R., and Króliczewski, J. (2019). Comprehensive review
correction for next-generation sequencing reads. Bioinformatics 31, 3476–3482. of antimicrobial activities of plant flavonoids. Phytochem. Rev. 18, 241–272.
doi: 10.1093/bioinformatics/btv401 doi: 10.1007/s11101-018-9591-z
Edwards, J. A., Santos-Medellin, C. M., Liechty, Z. S., Nguyen, B., Lurie, E., Eason, Greenblum, S., Turnbaugh, P. J., and Borenstein, E. (2012). Metagenomic systems
S., et al. (2018). Compositional shifts in root-associated bacterial and archaeal biology of the human gut microbiome reveals topological shifts associated
microbiota track the plant life cycle in field-grown rice. PLoS Biol. 16:e2003862. with obesity and inflammatory bowel disease. Proc. Natl. Acad. Sci. U.S.A. 109,
doi: 10.1371/journal.pbio.2003862 594–599. doi: 10.1073/pnas.1116053109
Escudero-Martinez, C., and Bulgarelli, D. (2019). Tracing the evolutionary routes Guerrieri, A., Dong, L., and Bouwmeester, H. J. (2019). Role and exploitation
of plant–microbiota interactions. Curr. Opin. Microbiol. 49, 34–40. doi: 10. of underground chemical signaling in plants. Pest Manag. Sci. 75, 2455–2463.
1016/j.mib.2019.09.013 doi: 10.1002/ps.5507
Etalo, D. W., Díez-Simón, C., de Vos, R. C. H. and Hall, R. D. (2018a). “Laser Gweon, H. S., Oliver, A., Taylor, J., Booth, T., Gibbs, M., Read, D. S., et al.
ablation electrospray ionization-mass spectrometry imaging (laesi-ms) for (2015). Pipits: an automated pipeline for analyses of fungal internal transcribed
spatially resolved plant metabolomics,” in Plant Metabolomics: Methods and spacer sequences from the illumina sequencing platform. Methods Ecol. Evol. 6,
Protocols, ed. C. António (New York, NY: Springer). 973–980. doi: 10.1111/2041-210x.12399
Etalo, D. W., Jeon, J. S., and Raaijmakers, J. M. (2018b). Modulation of plant Haney, C. H., Samuel, B. S., Bush, J., and Ausubel, F. M. (2015). Associations with
chemistry by beneficial root microbiota. Nat. Prod. Rep. 35, 398–409. doi: 10. rhizosphere bacteria can confer an adaptive advantage to plants. Nat. Plants
1039/c7np00057j 1:15051. doi: 10.1038/nplants.2015.51
Fabiańska, I., Gerlach, N., Almario, J., and Bucher, M. (2019). Plant-mediated Hansen, A. K., and Moran, N. A. (2014). The impact of microbial symbionts on
effects of soil phosphorus on the root-associated fungal microbiota in host plant utilization by herbivorous insects. Mol. Ecol. 23, 1473–1496. doi:
Arabidopsis thaliana. New Phytol. 221, 2123–2137. doi: 10.1111/nph.15538 10.1111/mec.12421
Fakhri, S., Moradi, S. Z., Farzaei, M. H., and Bishayee, A. (2020). Modulation of Hartman, K., van der Heijden, M. G., Roussely-Provent, V., Walser, J. C., and
dysregulated cancer metabolism by plant secondary metabolites: a mechanistic Schlaeppi, K. (2017). Deciphering composition and function of the root
review. Semin. Cancer Biol. doi: 10.1016/j.semcancer.2020.02.007 Online ahead microbiome of a legume plant. Microbiome 5:2. doi: 10.1186/s40168-016-0
of print 220-z
Helletsgruber, C., Dötterl, S., Ruprecht, U., and Junker, R. R. (2017). Epiphytic Köberl, M., Schmidt, R., Ramadan, E. M., Bauer, R., and Berg, G. (2013). The
bacteria alter floral scent emissions. J. Chem. Ecol. 43, 1073–1077. doi: 10.1007/ microbiome of medicinal plants: diversity and importance for plant growth,
s10886-017-0898-9 quality and health. Front. Microbiol. 4:400. doi: 10.3389/fmicb.2013.00400
Herrera Paredes, S., Gao, T., Law, T. F., Finkel, O. M., Mucyn, T., Koh, A., Molinaro, A., Stahlman, M., Khan, M. T., Schmidt, C., Manneras-Holm,
Teixeira, P., et al. (2018). Design of synthetic bacterial communities for L., et al. (2018). Microbially produced imidazole propionate impairs insulin
predictable plant phenotypes. PLoS Biol. 16:e2003962. doi: 10.1371/journal.pb signaling through mtorc1. Cell 175, 947.e17–961.e17. doi: 10.1016/j.cell.2018.
io.2003962 09.055
Hill, C. J., Lynch, D. B., Murphy, K., Ulaszewska, M., Jeffery, I. B., O’Shea, C. A., Kong, C. H., Zhang, S. Z., Li, Y. H., Xia, Z. C., Yang, X. F., Meiners, S. J., et al.
et al. (2017). Evolution of gut microbiota composition from birth to 24 weeks (2018). Plant neighbor detection and allelochemical response are driven by
in the infantmet cohort. Microbiome 5:4. doi: 10.1186/s40168-016-0213-y root-secreted signaling chemicals. Nat. Commun. 9:3867. doi: 10.1038/s41467-
Holmer, R., Rutten, L., Kohlen, W., van Velzen, R., and Geurts, R. (2017). 018-06429-1
“Commonalities in symbiotic plant-microbe signalling,” in Advances in Kong, H. G., Song, G. C., Sim, H.-J., and Ryu, C.-M. (2020). Achieving similar root
Botanical Research, ed. G. Becard (Cambridge, MA: Academic Press). microbiota composition in neighbouring plants through airborne signalling.
Hu, L., Robert, C. A. M., Cadot, S., Zhang, X., Ye, M., Li, B., et al. (2018). ISME J. 15, 397–408. doi: 10.1038/s41396-020-00759-z
Root exudate metabolites drive plant-soil feedbacks on growth and defense Koprivova, A., Schuck, S., Jacoby, R. P., Klinkhammer, I., Welter, B., Leson, L.,
by shaping the rhizosphere microbiota. Nat. Commun. 9:2738. doi: 10.1038/ et al. (2019). Root-specific camalexin biosynthesis controls the plant growth-
s41467-018-05122-7 promoting effects of multiple bacterial strains. Proc. Natl. Acad. Sci. U.S.A. 116,
Huang, A. C., Jiang, T., Liu, Y. X., Bai, Y. C., Reed, J., Qu, B., et al. 15735–15744. doi: 10.1073/pnas.1818604116
(2019). A specialized metabolic network selectively modulates Arabidopsis root Korenblum, E., and Aharoni, A. (2019). Phytobiome metabolism: beneficial soil
microbiota. Science 364:eaau6389. doi: 10.1126/science.aau6389 microbes steer crop plants’ secondary metabolism. Pest. Manag. Sci. 75, 2378–
Huang, W., Long, C., and Lam, E. (2018). Roles of plant-associated microbiota 2384. doi: 10.1002/ps.5440
in traditional herbal medicine. Trends Plant Sci. 23, 559–562. doi: 10.1016/j. Korenblum, E., Dong, Y., Szymanski, J., Panda, S., Jozwiak, A., Massalha, H., et al.
tplants.2018.05.003 (2020). Rhizosphere microbiome mediates systemic root metabolite exudation
Huang, Y. M., Zou, Y. N., and Wu, Q. S. (2017). Alleviation of drought stress by by root-to-root signaling. Proc. Natl. Acad. Sci. U.S.A. 117, 3874–3883. doi:
mycorrhizas is related to increased root h2o2 efflux in trifoliate orange. Sci Rep. 10.1073/pnas.1912130117
7:42335. doi: 10.1038/srep42335 Kosmacz, M., Sokołowska, E. M., Bouzaa, S., and Skirycz, A. (2020). Towards a
Iannucci, A., Fragasso, M., Beleggia, R., Nigro, F., and Papa, R. (2017). Evolution functional understanding of the plant metabolome. Curr. Opin. Plant Biol. 55,
of the crop rhizosphere: impact of domestication on root exudates in tetraploid 47–51. doi: 10.1016/j.pbi.2020.02.005
wheat (Triticum turgidum l.). Front. Plant Sci. 8:2124. doi: 10.3389/fpls.2017. Kostic, A. D., Gevers, D., Siljander, H., Vatanen, T., Hyotylainen, T., Hamalainen,
02124 A. M., et al. (2015). The dynamics of the human infant gut microbiome in
Ilhan, Z. E., DiBaise, J. K., Dautel, S. E., Isern, N. G., Kim, Y.-M., Hoyt, D. W., et al. development and in progression toward type 1 diabetes. Cell Host Microbe. 17,
(2020). Temporospatial shifts in the human gut microbiome and metabolome 260–273. doi: 10.1016/j.chom.2015.01.001
after gastric bypass surgery. NPJ Biofilms Microbiomes. 6:12. doi: 10.1038/ Kozuka, T., Sawada, Y., Imai, H., Kanai, M., Hirai, M. Y., Mano, S., et al.
s41522-020-0122-5 (2020). Regulation of sugar and storage oil metabolism by phytochrome during
Isah, T. (2019). Stress and defense responses in plant secondary metabolites de-etiolation. Plant Physiol. 182, 1114–1129. doi: 10.1104/pp.19.00535
production. Biol. Res. 52:39. doi: 10.1186/s40659-019-0246-3 Kudjordjie, E. N., Sapkota, R., Steffensen, S. K., Fomsgaard, I. S., and Nicolaisen,
Jacoby, R., Chen, L., Schwier, M., Koprivova, A., and Kopriva, S. (2020). Recent M. (2019). Maize synthesized benzoxazinoids affect the host associated
advances in the role of plant metabolites in shaping the root microbiome microbiome. Microbiome 7:59. doi: 10.1186/s40168-019-0677-7
[version 1; peer review: 3 approved]. F1000Res 9:F1000FacultyRev-151. doi: Kurtz, Z. D., Muller, C. L., Miraldi, E. R., Littman, D. R., Blaser, M. J.,
10.12688/f1000research.21796.1 and Bonneau, R. A. (2015). Sparse and compositionally robust inference of
Jacoby, R. P., Martyn, A., and Kopriva, S. (2018). Exometabolomic profiling of microbial ecological networks. PLoS Comput. Biol. 11:e1004226. doi: 10.1371/
bacterial strains as cultivated using Arabidopsis root extract as the sole carbon journal.pcbi.1004226
source. Mol. Plant Microbe Interact. 31, 803–813. doi: 10.1094/mpmi-10-17- Lamichhane, S., Sen, P., Dickens, A. M., Orešič, M., and Bertram, H. C. (2018). Gut
0253-r metabolome meets microbiome: a methodological perspective to understand
Jha, P., Panwar, J., and Jha, P. N. (2018). Mechanistic insights on plant root the relationship between host and microbe. Methods 149, 3–12. doi: 10.1016/j.
colonization by bacterial endophytes: a symbiotic relationship for sustainable ymeth.2018.04.029
agriculture. Environ. Sustain. 1, 25–38. doi: 10.1007/s42398-018-0011-5 Larsen, P. E., Collart, F. R., Field, D., Meyer, F., Keegan, K. P., Henry, C. S., et al.
Kai, M., Haustein, M., Molina, F., Petri, A., Scholz, B., and Piechulla, B. (2009). (2011). Predicted relative metabolomic turnover (prmt): determining metabolic
Bacterial volatiles and their action potential. Appl. Microbiol. Biotechnol. 81, turnover from a coastal marine metagenomic dataset. Microb. Inform. Exp. 1:4.
1001–1012. doi: 10.1007/s00253-008-1760-3 doi: 10.1186/2042-5783-1-4
Kamutando, C. N., Vikram, S., Kamgan-Nkuekam, G., Makhalanyane, T. P., Greve, Lavelle, A., and Sokol, H. (2020). Gut microbiota-derived metabolites as key actors
M., Le Roux, J. J., et al. (2019). The functional potential of the rhizospheric in inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 17, 223–237.
microbiome of an invasive tree species, acacia dealbata. Microb. Ecol. 77, doi: 10.1038/s41575-019-0258-z
191–200. doi: 10.1007/s00248-018-1214-0 Lebeis, S. L., Paredes, S. H., Lundberg, D. S., Breakfield, N., Gehring, J., McDonald,
Kang, S. M., Khan, A. L., Waqas, M., Asaf, S., Lee, K. E., Park, Y. G., et al. M., et al. (2015). Plant microbiome. Salicylic acid modulates colonization of the
(2019). Integrated phytohormone production by the plant growth-promoting root microbiome by specific bacterial taxa. Science 349, 860–864. doi: 10.1126/
rhizobacterium Bacillus tequilensis SSB07 induced thermotolerance in soybean. science.aaa8764
J. Plant Interact. 14, 416–423. doi: 10.1080/17429145.2019.1640294 Lenzewski, N., Mueller, P., Meier, R. J., Liebsch, G., Jensen, K., and Koop-Jakobsen,
Kessler, A., and Kalske, A. (2018). Plant secondary metabolite diversity and species K. (2018). Dynamics of oxygen and carbon dioxide in rhizospheres of lobelia
interactions. Annu. Rev. Ecol. Evol. Syst. 49, 115–138. doi: 10.1146/annurev- dortmanna – a planar optode study of belowground gas exchange between
ecolsys-110617-062406 plants and sediment. New Phytol. 218, 131–141. doi: 10.1111/nph.14973
Kniskern, J. M., Traw, M. B., and Bergelson, J. (2007). Salicylic acid and Li, B., Li, Y.-Y., Wu, H.-M., Zhang, F.-F., Li, C.-J., Li, X.-X., et al. (2016).
jasmonic acid signaling defense pathways reduce natural bacterial diversity on Root exudates drive interspecific facilitation by enhancing nodulation and
Arabidopsis thaliana. Mol. Plant Microbe Interact. 20, 1512–1522. doi: 10.1094/ n2 fixation. Proc. Natl. Acad. Sci. U.S.A. 113, 6496–6501. doi: 10.1073/pnas.
mpmi-20-12-1512 1523580113
Liang, D., Li, M., Wei, R., Wang, J., Li, Y., Jia, W., et al. (2019). Strategy for microbiota with increasing dietary grain in a goat model. Environ. Microbiol.
intercorrelation identification between metabolome and microbiome. Anal. 18, 525–541. doi: 10.1111/1462-2920.12724
Chem. 91, 14424–14432. doi: 10.1021/acs.analchem.9b02948 Mariano, D. C., Pereira, F. L., Aguiar, E. L., Oliveira, L. C., Benevides, L.,
Liu, H., and Brettell, L. E. (2019). Plant defense by voc-induced microbial priming. Guimaraes, L. C., et al. (2016). Simba: a web tool for managing bacterial genome
Trends Plant Sci. 24, 187–189. doi: 10.1016/j.tplants.2019.01.008 assembly generated by ion pgm sequencing technology. BMC Bioinformatics
Liu, H., Brettell, L. E., Qiu, Z., and Singh, B. K. (2020). Microbiome-mediated stress 17:456. doi: 10.1186/s12859-016-1344-7
resistance in plants. Trends Plant Sci. 25, 733–743. doi: 10.1016/j.tplants.2020. Massalha, H., Korenblum, E., Malitsky, S., Shapiro, O. H., and Aharoni, A. (2017).
03.014 Live imaging of root-bacteria interactions in a microfluidics setup. Proc. Natl.
Liu, H., Carvalhais, L. C., Schenk, P. M., and Dennis, P. G. (2017). Effects of Acad. Sci. U.S.A. 114, 4549–4554. doi: 10.1073/pnas.1618584114
jasmonic acid signalling on the wheat microbiome differ between body sites. Mastan, A., Bharadwaj, R. K. B., Kushwaha, R. K., and Vivek Babu, C. S. (2019).
Sci. Rep. 7:41766. doi: 10.1038/srep41766 Functional fungal endophytes in coleus forskohlii regulate labdane diterpene
Liu, Y. X., Qin, Y., and Bai, Y. (2019). Reductionist synthetic community biosynthesis for elevated forskolin accumulation in roots. Microb. Ecol. 78,
approaches in root microbiome research. Curr. Opin. Microbiol. 49, 97–102. 914–926. doi: 10.1007/s00248-019-01376-w
doi: 10.1016/j.mib.2019.10.010 Masteling, R., Lombard, L., de Boer, W., Raaijmakers, J. M., and Dini-Andreote,
Liu, Y. X., Qin, Y., Chen, T., Lu, M., Qian, X., Guo, X., et al. (2020). A practical F. (2019). Harnessing the microbiome to control plant parasitic weeds. Curr.
guide to amplicon and metagenomic analysis of microbiome data. Protein Cell Opin. Microbiol. 49, 26–33. doi: 10.1016/j.mib.2019.09.006
doi: 10.1007/s13238-020-00724-8 Online ahead of print Masuda, K., Abouleila, Y., Ali, A., and Yanagida, T. and Masujima, T. (2018).
Lock, E. F., Hoadley, K. A., Marron, J. S., and Nobel, A. B. (2013). Joint and “Live single-cell mass spectrometry (lsc-ms) for plant metabolomics,” in Plant
individual variation explained (jive) for integrated analysis of multiple data Metabolomics: Methods and Protocols, eds C. António (New York, NY: Springer
types. Ann. Appl. Stat. 7, 523–542. doi: 10.1214/12-AOAS597 New York).
Lovell, D., Pawlowsky-Glahn, V., Egozcue, J. J., Marguerat, S., and Bahler, J. (2015). McGregor, K., Labbe, A., and Greenwood, C. M. T. (2020). Mdine: a model
Proportionality: a valid alternative to correlation for relative data. PLoS Comput. to estimate differential co-occurrence networks in microbiome studies.
Biol. 11:e1004075. doi: 10.1371/journal.pcbi.1004075 Bioinformatics 36, 1840–1847. doi: 10.1093/bioinformatics/btz824
Lu, W., Su, X., Klein, M. S., Lewis, I. A., Fiehn, O., and Rabinowitz, J. D. McHardy, I. H., Goudarzi, M., Tong, M., Ruegger, P. M., Schwager, E., Weger,
(2017). Metabolite measurement: pitfalls to avoid and practices to follow. J. R., et al. (2013). Integrative analysis of the microbiome and metabolome
Annu. Rev. Biochem. 86, 277–304. doi: 10.1146/annurev-biochem-061516-04 of the human intestinal mucosal surface reveals exquisite inter-relationships.
4952 Microbiome 1:17. doi: 10.1186/2049-2618-1-17
Lucaciu, R., Pelikan, C., Gerner, S. M., Zioutis, C., Köstlbacher, S., Marx, H., et al. McIver, L. J., Abu-Ali, G., Franzosa, E. A., Schwager, R., Morgan, X. C., Waldron,
(2019). A bioinformatics guide to plant microbiome analysis. Front. Plant Sci. L., et al. (2018). Biobakery: a meta’omic analysis environment. Bioinformatics
10:1313. doi: 10.3389/fpls.2019.01313 34, 1235–1237. doi: 10.1093/bioinformatics/btx754
Lundberg, D. S., and Teixeira, P. (2018). Root-exuded coumarin shapes the root Mehmood, A., Hussain, A., Irshad, M., Hamayun, M., Iqbal, A., Tawab, A., et al.
microbiome. Proc. Natl. Acad. Sci. U.S.A. 115, 5629–5631. doi: 10.1073/pnas. (2020). Yucasin and cinnamic acid inhibit iaa and flavonoids biosynthesis
1805944115 minimizing interaction between maize and endophyteaspergillus nomius.
Luo, P., Yin, P., Zhang, W., Zhou, L., Lu, X., Lin, X., et al. (2016). Symbiosis 12, 149–160. doi: 10.1007/s13199-020-00690-z
Optimization of large-scale pseudotargeted metabolomics method based on Melnik, A. V., da Silva, R. R., Hyde, E. R., Aksenov, A. A., Vargas, F., Bouslimani,
liquid chromatography–mass spectrometry. J. Chromatogr. A 1437, 127–136. A., et al. (2017). Coupling targeted and untargeted mass spectrometry for
doi: 10.1016/j.chroma.2016.01.078 metabolome-microbiome-wide association studies of human fecal samples.
Maggini, V., Bandeira Reidel, R. V., De Leo, M., Mengoni, A., Gallo, E. R., Miceli, Anal. Chem. 89, 7549–7559. doi: 10.1021/acs.analchem.7b01381
E., et al. (2019a). Volatile profile of echinacea purpurea plants after in vitro Mendes-Soares, H., Mundy, M., Soares, L. M., and Chia, N. (2016). Mminte: an
endophyte infection. Nat. Prod. Res. 34, 2232–2237. doi: 10.1080/14786419. application for predicting metabolic interactions among the microbial species
2019.1579810 in a community. BMC Bioinformatics 17:343. doi: 10.1186/s12859-016-1230-3
Maggini, V., De Leo, M., Granchi, C., Tuccinardi, T., Mengoni, A., Gallo, E. R., Millet, L. J., Aufrecht, J., Labbe, J., Uehling, J., Vilgalys, R., Estes, M. L., et al.
et al. (2019b). The influence of echinacea purpurea leaf microbiota on chicoric (2019). Increasing access to microfluidics for studying fungi and other branched
acid level. Sci. Rep. 9:10897. doi: 10.1038/s41598-019-47329-8 biological structures. Fungal Biol. Biotechnol. 6:1. doi: 10.1186/s40694-019-
Maggini, V., De Leo, M., Mengoni, A., Gallo, E. R., Miceli, E., Reidel, R. V. B., 0071-z
et al. (2017). Plant-endophytes interaction influences the secondary metabolism Misra, B. B. (2020). The connection and disconnection between microbiome and
in echinacea purpurea (l.) moench: an in vitro model. Sci. Rep. 7:16924. doi: metabolome: a critical appraisal in clinical research. Biol. Res. Nurs. 22, 561–576.
10.1038/s41598-017-17110-w doi: 10.1177/1099800420903083
Maggini, V., Mengoni, A., Bogani, P., Firenzuoli, F., and Fani, R. (2020). Promoting Morton, J. T., Aksenov, A. A., Nothias, L. F., Foulds, J. R., Quinn, R. A.,
model systems of microbiota-medicinal plant interactions. Trends Plant Sci. 25, Badri, M. H., et al. (2019). Learning representations of microbe-metabolite
223–225. doi: 10.1016/j.tplants.2019.12.013 interactions. Nat. Methods 16, 1306–1314. doi: 10.1038/s41592-019-0616-3
Maggini, V., Miceli, E., Fagorzi, C., Maida, I., Fondi, M., Perrin, E., et al. (2018). Nascimento, F. X., Rossi, M. J., and Glick, B. R. (2018). Ethylene and 1-
Antagonism and antibiotic resistance drive a species-specific plant microbiota aminocyclopropane-1-carboxylate (acc) in plant–bacterial interactions. Front.
differentiation in echinacea spp. FEMS Microbiol. Ecol. 94, 1–18. doi: 10.1093/ Plant Sci. 9:114. doi: 10.3389/fpls.2018.00114
femsec/fiy118 Nasir, F., Li, W., Tran, L.-S. P., and Tian, C. (2020). Does karrikin signaling shape
Magnúsdóttir, S., Heinken, A., Kutt, L., Ravcheev, D. A., Bauer, E., Noronha, A., the rhizomicrobiome via the strigolactone biosynthetic pathway? Trends Plant
et al. (2017). Generation of genome-scale metabolic reconstructions for 773 Sci. 25, 1184–1187. doi: 10.1016/j.tplants.2020.08.005
members of the human gut microbiota. Nat. Biotechnol. 35, 81–89. doi: 10.1038/ Nasir, F., Shi, S., Tian, L., Chang, C., Ma, L., Li, X., et al. (2019). Strigolactones
nbt.3703 shape the rhizomicrobiome in rice (Oryza sativa). Plant Sci. 286, 118–133.
Mallick, H., Franzosa, E. A., McLver, L. J., Banerjee, S., Sirota-Madi, A., Kostic, doi: 10.1016/j.plantsci.2019.05.016
A. D., et al. (2019). Predictive metabolomic profiling of microbial communities Naylor, D., and Coleman-Derr, D. (2017). Drought stress and root-associated
using amplicon or metagenomic sequences. Nat. Commun. 10:3136. doi: 10. bacterial communities. Front. Plant Sci. 8:2223. doi: 10.3389/fpls.2017.0
1038/s41467-019-10927-1 2223
Mao, S.-Y., Huo, W.-J., and Zhu, W.-Y. (2016). Microbiome–metabolome analysis Nemet, I., Saha, P. P., Gupta, N., Zhu, W., Romano, K. A., Skye, S. M.,
reveals unhealthy alterations in the composition and metabolism of ruminal et al. (2020). A cardiovascular disease-linked gut microbial metabolite acts
via adrenergic receptors. Cell 180, 862.e22–877.e22. doi: 10.1016/j.cell.2020. Ray, S., Singh, J., Rajput, R. S., Yadav, S., Singh, S., and Singh, H. B. (2019).
02.016 “A thorough comprehension of host endophytic interaction entailing the
Ni, Y., Yu, G., Chen, H., Deng, Y., Wells, P. M., Steves, C. J., et al. (2020). biospherical benefits: a metabolomic perspective,” in Endophytes and Secondary
M2ia: a web server for microbiome and metabolome integrative analysis. Metabolites, ed. S. Jha (Cham: Springer International Publishing).
Bioinformatics. 36, 3493–3498. doi: 10.1093/bioinformatics/btaa188 Ray, T., Pandey, S. S., Pandey, A., Srivastava, M., Shanker, K., and Kalra, A.
Nilsson, R. H., Anslan, S., Bahram, M., Wurzbacher, C., Baldrian, P., and Tedersoo, (2019). Endophytic consortium with diverse gene-regulating capabilities of
L. (2019). Mycobiome diversity: high-throughput sequencing and identification benzylisoquinoline alkaloids biosynthetic pathway can enhance endogenous
of fungi. Nat. Rev. Microbiol. 17, 95–109. doi: 10.1038/s41579-018-0116-y morphine biosynthesis in papaver somniferum. Front. Microbiol. 10:925. doi:
Noecker, C., Chiu, H.-C., McNally, C. P., and Borenstein, E. (2019). Defining 10.3389/fmicb.2019.00925
and evaluating microbial contributions to metabolite variation in microbiome- Raza, W., Wang, J., Jousset, A., Friman, V.-P., Mei, X., Wang, S., et al. (2020).
metabolome association studies. mSystems 4:e579-19. doi: 10.1128/mSystems. Bacterial community richness shifts the balance between volatile organic
00579-19 compound-mediated microbe–pathogen and microbe–plant interactions. Proc.
Noecker, C., Eng, A., Srinivasan, S., Theriot, C. M., Young, V. B., Jansson, J. K., R. Soc. B Biol. Sci. 287:20200403. doi: 10.1098/rspb.2020.0403
et al. (2016). Metabolic model-based integration of microbiome taxonomic Reshef, D. N., Reshef, Y. A., Finucane, H. K., Grossman, S. R., McVean, G.,
and metabolomic profiles elucidates mechanistic links between ecological and Turnbaugh, P. J., et al. (2011). Detecting novel associations in large data sets.
metabolic variation. mSystems 1:e00013-15. doi: 10.1128/mSystems.00013-15 Science 334, 1518–1524. doi: 10.1126/science.1205438
Noirot-Gros, M. F., Shinde, S. V., Akins, C., Johnson, J. L., Zerbs, S., Wilton, R., Rodriguez, P. A., Rothballer, M., Chowdhury, S. P., Nussbaumer, T., Gutjahr, C.,
et al. (2020). Functional imaging of microbial interactions with tree roots using and Falter-Braun, P. (2019). Systems biology of plant-microbiome interactions.
a microfluidics setup. Front. Plant Sci. 11:408. doi: 10.3389/fpls.2020.00408 Mol. Plant 12, 804–821. doi: 10.1016/j.molp.2019.05.006
Okutani, F., Hamamoto, S., Aoki, Y., Nakayasu, M., Nihei, N., Nishimura, T., Rognes, T., Flouri, T., Nichols, B., Quince, C., and Mahe, F. (2016). Vsearch: a
et al. (2020). Rhizosphere modelling reveals spatiotemporal distribution of versatile open source tool for metagenomics. PeerJ. 4:e2584. doi: 10.7717/peerj.
daidzein shaping soybean rhizosphere bacterial community. Plant Cell Environ. 2584
43, 1036–1046. doi: 10.1111/pce.13708 Sasse, J., Martinoia, E., and Northen, T. (2018). Feed your friends: do plant exudates
Ortíz-Castro, R., Contreras-Cornejo, H. A., Macías-Rodríguez, L., and López- shape the root microbiome? Trends Plant Sci. 23, 25–41. doi: 10.1016/j.tplants.
Bucio, J. (2009). The role of microbial signals in plant growth and development. 2017.09.003
Plant Signal. Behav. 4, 701–712. doi: 10.4161/psb.4.8.9047 Schandry, N., and Becker, C. (2020). Allelopathic plants: models for studying
Pagnani, G., Pellegrini, M., Galieni, A., D’Egidio, S., Matteucci, F., Ricci, A., et al. plant–interkingdom interactions. Trends Plant Sci. 25, 176–185. doi: 10.1016/
(2018). Plant growth-promoting rhizobacteria (pgpr) in cannabis sativa ‘finola’ j.tplants.2019.11.004
cultivation: an alternative fertilization strategy to improve plant growth and Schenkel, D., Deveau, A., Niimi, J., Mariotte, P., Vitra, A., Meisser, M., et al. (2019).
quality characteristics. Indust. Crops Prod. 123, 75–83. doi: 10.1016/j.indcrop. Linking soil’s volatilome to microbes and plant roots highlights the importance
2018.06.033 of microbes as emitters of belowground volatile signals. Environ. Microbiol.
Pangesti, N., Reichelt, M., van de Mortel, J. E., Kapsomenou, E., Gershenzon, J., doi: 10.1111/1462-2920.14599 Online ahead of print
van Loon, J. J., et al. (2016). Jasmonic acid and ethylene signaling pathways Schlechter, R. O., Miebach, M., and Remus-Emsermann, M. N. P. (2019). Driving
regulate glucosinolate levels in plants during rhizobacteria-induced systemic factors of epiphytic bacterial communities: a review. J. Adv. Res. 19, 57–65.
resistance against a leaf-chewing herbivore. J. Chem. Ecol. 42, 1212–1225. doi: doi: 10.1016/j.jare.2019.03.003
10.1007/s10886-016-0787-7 Schulz-Bohm, K., Gerards, S., Hundscheid, M., Melenhorst, J., de Boer, W., and
Pascale, A., Proietti, S., Pantelides, I. S., and Stringlis, I. A. (2020). Modulation of the Garbeva, P. (2018). Calling from distance: attraction of soil bacteria by plant
root microbiome by plant molecules: the basis for targeted disease suppression root volatiles. ISME J. 12, 1252–1262. doi: 10.1038/s41396-017-0035-3
and plant growth promotion. Front. Plant Sci. 10:1741. doi: 10.3389/fpls.2019. Schütz, V., Bigler, L., Girel, S., Laschke, L., Sicker, D., and Schulz, M.
01741 (2019). Conversions of benzoxazinoids and downstream metabolites by soil
Pei, Y. C., Siemann, E., Tian, B. L., and Ding, J. Q. (2020). Root flavonoids are microorganisms. Front. Ecol. Evol. 7:238. doi: 10.3389/fevo.2019.00238
related to enhanced amf colonization of an invasive tree. AoB Plants 12:laa002. Shtark, O. Y., Shishova, M. F., Povydysh, M. N., Avdeeva, G. S., Zhukov, V. A.,
doi: 10.1093/aobpla/plaa002 and Tikhonovich, I. A. (2018). Strigolactones as regulators of symbiotrophy of
Peñuelas, J., Farré-Armengol, G., Llusia, J., Gargallo-Garriga, A., Rico, L., Sardans, plants and microorganisms. Russ. J. Plant Physiol. 65, 151–167. doi: 10.1134/
J., et al. (2014). Removal of floral microbiota reduces floral terpene emissions. S1021443718020073
Sci. Rep. 4:6727. doi: 10.1038/srep06727 Smilde, A. K., Måge, I., Næs, T., Hankemeier, T., Lips, M. A., Kiers, H. A. L., et al.
Perez-Jaramillo, J. E., de Hollander, M., Ramirez, C. A., Mendes, R., Raaijmakers, (2017). Common and distinct components in data fusion. J. Chemom. 31:e2900.
J. M., and Carrion, V. J. (2019). Deciphering rhizosphere microbiome assembly doi: 10.1002/cem.2900
of wild and modern common bean (Phaseolus vulgaris) in native and Sokol, N. W., Kuebbing, S. E., Karlsen-Ayala, E., and Bradford, M. A. (2019).
agricultural soils from colombia. Microbiome 7:114. doi: 10.1186/s40168-019- Evidence for the primacy of living root inputs, not root or shoot litter, in
0727-1 forming soil organic carbon. New Phytol. 221, 233–246. doi: 10.1111/nph.15361
Peter, A., Pola, S. P., Sandeep, B., and Rao, B. (2019). Antimicrobial and Anti- Stassen, M. J. J., Hsu, S.-H., Pieterse, C. M. J., and Stringlis, I. A. (2020). Coumarin
Quorum Sensing Activities of Medicinal Plants. Singapore: Springer. communication along the microbiome–root–shoot axis. Trends Plant Sci. 26,
Petriacq, P., Williams, A., Cotton, A., McFarlane, A. E., Rolfe, S. A., and Ton, J. 169–183. doi: 10.1016/j.tplants.2020.09.008
(2017). Metabolite profiling of non-sterile rhizosphere soil. Plant J. 92, 147–162. Stefanowicz, A. M., Stanek, M., Nobis, M., and Zubek, S. (2017). Few effects of
doi: 10.1111/tpj.13639 invasive plants reynoutria japonica, rudbeckia laciniata and solidago gigantea
Piasecka, A., Jedrzejczak-Rey, N., and Bednarek, P. (2015). Secondary metabolites on soil physical and chemical properties. Sci. Total Environ. 574, 938–946.
in plant innate immunity: conserved function of divergent chemicals. New doi: 10.1016/j.scitotenv.2016.09.120
Phytol. 206, 948–964. doi: 10.1111/nph.13325 Stringlis, I. A., de Jonge, R., and Pieterse, C. M. J. (2019). The age of coumarins in
Pini, F., East, A. K., Appia-Ayme, C., Tomek, J., Karunakaran, R., Mendoza-Suarez, plant-microbe interactions. Plant Cell Physiol. 60, 1405–1419. doi: 10.1093/pcp/
M., et al. (2017). Bacterial biosensors for in vivo spatiotemporal mapping of root pcz076
secretion. Plant Physiol. 174, 1289–1306. doi: 10.1104/pp.16.01302 Stringlis, I. A., Yu, K., Feussner, K., de Jonge, R., Van Bentum, S., Van Verk, M. C.,
Rajniak, J., Giehl, R. F. H., Chang, E., Murgia, I., von Wiren, N., and Sattely, E. S. et al. (2018). Myb72-dependent coumarin exudation shapes root microbiome
(2018). Biosynthesis of redox-active metabolites in response to iron deficiency assembly to promote plant health. Proc. Natl. Acad. Sci. U.S.A. 115, E5213–
in plants. Nat. Chem. Biol. 14, 442–450. doi: 10.1038/s41589-018-0019-2 E5222. doi: 10.1073/pnas.1722335115
Sugiyama, A. (2019). The soybean rhizosphere: metabolites, microbes, and beyond- type iii secretion system to inhibit bacterial virulence. Cell Host Microbe 27,
a review. J. Adv. Res. 19, 67–73. doi: 10.1016/j.jare.2019.03.005 601.e7–613.e7. doi: 10.1016/j.chom.2020.03.004
Sugiyama, A., and Yazaki, K. (2014). Flavonoids in plant rhizospheres: secretion, Wasternack, C., and Hause, B. (2013). Jasmonates: biosynthesis, perception, signal
fate and their effects on biological communication. Plant Biotechnol. 31, 431– transduction and action in plant stress response, growth and development.
443. doi: 10.5511/plantbiotechnology.14.0917a An update to the 2007 review in annals of botany. Ann. Bot. 111, 1021–1058.
Szoboszlay, M., White-Monsant, A., and Moe, L. A. (2016). The effect of root doi: 10.1093/aob/mct067
exudate 7,4’-dihydroxyflavone and naringenin on soil bacterial community Weiss, S., Van Treuren, W., Lozupone, C., Faust, K., Friedman, J., Deng, Y., et al.
structure. PLoS One 11:e0146555. doi: 10.1371/journal.pone.0146555 (2016). Correlation detection strategies in microbial data sets vary widely in
Taghinasab, M., and Jabaji, S. (2020). Cannabis microbiome and the sensitivity and precision. ISME J. 10, 1669–1681. doi: 10.1038/ismej.2015.235
role of endophytes in modulating the production of secondary White, L. J., Ge, X., Brözel, V. S., and Subramanian, S. (2017). Root isoflavonoids
metabolites: an overview. Microorganisms 8:355. doi: 10.3390/microorganis and hairy root transformation influence key bacterial taxa in the soybean
ms8030355 rhizosphere. Environ. Microbiol. 19, 1391–1406. doi: 10.1111/1462-2920.13602
Tahir, A. T., Fatmi, Q., Nosheen, A., Imtiaz, M., and Khan, S (2019). “Metabolomic Williams, A., and de Vries, F. T. (2020). Plant root exudation under drought:
approaches in plant research,” in Essentials of Bioinformatics, Volume III: implications for ecosystem functioning. New Phytol. 225, 1899–1905. doi: 10.
In Silico Life Sciences: Agriculture, eds K. R. Hakeem, N. A. Shaik, and B. 1111/nph.16223
Banaganapalli (Cham: Springer International Publishing). Xu, L., Naylor, D., Dong, Z., Simmon, T., Pierroz, G., Hixson, K. K., et al. (2018).
Tian, T., Reverdy, A., She, Q., Sun, B., and Chai, Y. (2020). The role of rhizodeposits Drought delays development of the sorghum root microbiome and enriches for
in shaping rhizomicrobiome. Environ. Microbiol. Rep. 12, 160–172. doi: 10. monoderm bacteria. Proc. Natl. Acad. Sci. U.S.A. 115:E4952. doi: 10.1073/pnas.
1111/1758-2229.12816 1807275115
Tian, Y., Amand, S., Buisson, D., Kunz, C., Hachette, F., Dupont, J., et al. (2014). Yang, L., Wen, K. S., Ruan, X., Zhao, Y. X., Wei, F., and Wang, Q. (2018). Response
The fungal leaf endophyte paraconiothyrium variabile specifically metabolizes of plant secondary metabolites to environmental factors. Molecules 23:762.
the host-plant metabolome for its own benefit. Phytochemistry 108, 95–101. doi: 10.3390/molecules23040762
doi: 10.1016/j.phytochem.2014.09.021 Yang, W., Zhang, D., Cai, X., Xia, L., Luo, Y., Cheng, X., et al. (2019). Significant
Tidke, S. A., Kiran, S., Giridhar, P. and Gokare, R. A. (2019). “Current alterations in soil fungal communities along a chronosequence of spartina
understanding and future perspectives of endophytic microbes vis- alterniflora invasion in a chinese yellow sea coastal wetland. Sci. Total Environ.
a-vis production of secondary metabolites,” in Endophytes and 693:133548. doi: 10.1016/j.scitotenv.2019.07.354
Secondary Metabolites, ed. S. Jha (Cham: Springer International You, M., Fang, S. M., MacDonald, J., Xu, J., and Yuan, Z. C. (2020). Isolation and
Publishing). characterization of Burkholderia cenocepacia CR318, a phosphate solubilizing
Trda, L., Janda, M., Mackova, D., Pospichalova, R., Dobrev, P. I., Burketova, L., bacterium promoting corn growth. Microbiol. Res. 233:126395. doi: 10.1016/j.
et al. (2019). Dual mode of the saponin aescin in plant protection: antifungal micres.2019.126395
agent and plant defense elicitor. Front. Plant Sci. 10:1448. doi: 10.3389/fpls.2019. Youens-Clark, K., Bomhoff, M., Ponsero, A. J., Wood-Charlson, E. M., Lynch, J.,
01448 Choi, I., et al. (2019). Imicrobe: tools and data-dreaiven discovery platform for
Ullrich, C. I., Aloni, R., Saeed, M. E. M., Ullrich, W., and Efferth, T. (2019). the microbiome sciences. Gigascience 8:giz083. doi: 10.1093/gigascience/giz083
Comparison between tumors in plants and human beings: mechanisms Yuan, J., Zhao, J., Wen, T., Zhao, M., Li, R., Goossens, P., et al. (2018). Root
of tumor development and therapy with secondary plant metabolites. exudates drive the soil-borne legacy of aboveground pathogen infection.
Phytomedicine 64:153081. doi: 10.1016/j.phymed.2019.153081 Microbiome 6:156. doi: 10.1186/s40168-018-0537-x
van der Kloet, F. M., Sebastian-Leon, P., Conesa, A., Smilde, A. K., and Westerhuis, Zhalnina, K., Louie, K. B., Hao, Z., Mansoori, N., da Rocha, U. N., Shi, S., et al.
J. A. (2016). Separating common from distinctive variation. BMC Bioinformatics (2018). Dynamic root exudate chemistry and microbial substrate preferences
17(Suppl. 5):195. doi: 10.1186/s12859-016-1037-2 drive patterns in rhizosphere microbial community assembly. Nat. Microbiol. 3,
Van Deynze, A., Zamora, P., Delaux, P. M., Heitmann, C., Jayaraman, D., Rajasekar, 470–480. doi: 10.1038/s41564-018-0129-3
S., et al. (2018). Nitrogen fixation in a landrace of maize is supported by a Zhan, Z. J., Tian, T., Xu, Y. L., Yu, H. F., Zhang, C. X., Zhang, Z. D., et al. (2019).
mucilage-associated diazotrophic microbiota. PLoS Biol. 16:e2006352. doi: 10. Biotransformation of huperzine b by a fungal endophyte of huperzia serrata.
1371/journal.pbio.2006352 Chem. Biodivers. 16:e1900299. doi: 10.1002/cbdv.201900299
Varoquaux, N., Cole, B., Gao, C., Pierroz, G., Baker, C. R., Patel, D., et al. (2019). Zhang, B., Zhang, J., Liu, Y., Shi, P., and Wei, G. (2018). Co-occurrence patterns of
Transcriptomic analysis of field-droughted sorghum from seedling to maturity soybean rhizosphere microbiome at a continental scale. Soil Biol. Biochem. 118,
reveals biotic and metabolic responses. Proc Natl Acad Sci U S A. doi: 10.1073/ 178–186. doi: 10.1016/j.soilbio.2017.12.011
pnas.1907500116 Online ahead of print Zhang, H., Kim, M. S., Krishnamachari, V., Payton, P., Sun, Y., Crimson, M., et al.
Venturi, V., and Keel, C. (2016). Signaling in the rhizosphere. Trends Plant Sci. 21, (2007). Rhizobacterial volatile emissions regulate auxin homeostasis and cell
187–198. doi: 10.1016/j.tplants.2016.01.005 expansion in Arabidopsis. Planta 226, 839–851. doi: 10.1007/s00425-007-0530-
Verbeek, J. D., and Kotanen, P. M. (2019). Soil-mediated impacts of an invasive 2
thistle inhibit the recruitment of certain native plants. Oecologia 190, 619–628. Zhang, J., Liu, Y. X., Zhang, N., Hu, B., Jin, T., Xu, H., et al. (2019). Nrt1.1b is
doi: 10.1007/s00442-019-04435-8 associated with root microbiota composition and nitrogen use in field-grown
Vives-Peris, V., de Ollas, C., Gomez-Cadenas, A., and Perez-Clemente, R. M. rice. Nat. Biotechnol. 37, 676–684. doi: 10.1038/s41587-019-0104-4
(2020). Root exudates: from plant to rhizosphere and beyond. Plant Cell Rep. Zhang, Y., Li, S. S., Li, H. X., Wang, R. R., Zhang, K. Q., and Xu, J. (2020).
39, 3–17. doi: 10.1007/s00299-019-02447-5 Fungal-nematode interactions: diversity, ecology and biocontrol prospects in
Voges, M., Bai, Y., Schulze-Lefert, P., and Sattely, E. S. (2019). Plant-derived agriculture. J. Fungi. 6:206. doi: 10.3390/jof6040206
coumarins shape the composition of an Arabidopsis synthetic root microbiome. Zhang, Y., Xu, J., Riera, N., Jin, T., Li, J., and Wang, N. (2017). Huanglongbing
Proc. Natl. Acad. Sci. U.S.A. 116, 12558–12565. doi: 10.1073/pnas.1820691116 impairs the rhizosphere-to-rhizoplane enrichment process of the citrus root-
Wang, D., Xu, Z., Zhang, G., Xia, L., Dong, X., Li, Q., et al. (2019). A genomic island associated microbiome. Microbiome 5:97. doi: 10.1186/s40168-017-0304-4
in a plant beneficial rhizobacterium encodes novel antimicrobial fatty acids Zheng, Q., Bartow-McKenney, C., Meisel, J. S., and Grice, E. A. (2018). Hmmufotu:
and a self-protection shield to enhance its competition. Environ. Microbiol. an hmm and phylogenetic placement based ultra-fast taxonomic assignment
doi: 10.1111/1462-2920.14683 Online ahead of print and otu picking tool for microbiome amplicon sequencing studies. Genome
Wang, P., and Niu, B. (2019). Plant specialized metabolites modulate root Biol. 19:82. doi: 10.1186/s13059-018-1450-0
microbiomes. Sci. China Life Sci. 62, 1111–1113. doi: 10.1007/s11427-019- Zhou, F., Emonet, A., Dénervaud Tendon, V., Marhavy, P., Wu, D., Lahaye, T.,
9579-6 et al. (2020). Co-incidence of damage and microbial patterns controls localized
Wang, W., Yang, J., Zhang, J., Liu, Y. X., Tian, C., Qu, B., et al. (2020). An immune responses in roots. Cell 180, 440.e18–453.e18. doi: 10.1016/j.cell.2020.
Arabidopsis secondary metabolite directly targets expression of the bacterial 01.013
Zhou, F., and Pichersky, E. (2020). More is better: the diversity of terpene Conflict of Interest: The authors declare that the research was conducted in the
metabolism in plants. Curr. Opin. Plant Biol. 55, 1–10. doi: 10.1016/j.pbi.2020. absence of any commercial or financial relationships that could be construed as a
01.005 potential conflict of interest.
Zhou, J.-L., Xu, J., Jiao, A.-G., Yang, L., Chen, J., Callac, P., et al. (2019). Patterns
of PCR amplification artifacts of the fungal barcode marker in a hybrid Copyright © 2021 Pang, Chen, Wang, Gao, Li, Guo, Xu and Cheng. This is an
mushroom. Front. Microbiol. 10:2686. doi: 10.3389/fmicb.2019.02686 open-access article distributed under the terms of the Creative Commons Attribution
Zhou, J. Y., Sun, K., Chen, F., Yuan, J., Li, X., and Dai, C. C. (2018). License (CC BY). The use, distribution or reproduction in other forums is permitted,
Endophytic Pseudomonas induces metabolic flux changes that enhance provided the original author(s) and the copyright owner(s) are credited and that the
medicinal sesquiterpenoid accumulation in atractylodes lancea. original publication in this journal is cited, in accordance with accepted academic
Plant Physiol. Biochem. 130, 473–481. doi: 10.1016/j.plaphy.2018.07. practice. No use, distribution or reproduction is permitted which does not comply
016 with these terms.