Microbiome and Diseases: Pathogen Infection: Christine Josenhans and Guntram A. Grassl

Microbiome and Diseases: Pathogen
Infection 14
Christine Josenhans and Guntram A. Grassl
Abstract how intestinal pathogenic agents can interact

The host and the intestinal microbiota contrib- with both the host and the microbiota in order
ute in manifold ways to an immune balance to promote their own expansion, to overcome
and defense against diseases and pathogens. the defenses by the resident microbiota and the
Infectious diseases of the intestine are major mucosal barrier, and how they finally cause
diseases which severely threaten individual disease. This chapter also introduces novel
and global health. Enteropathogenic agents ways how to treat intestinal infections by
causing infectious diseases have evolved spe- addressing the microbiota.
cific tactics how they interact with the host and
with the microbiota simultaneously. This
chapter characterizes the main players of the
14.1 The Intestinal Niche
intestinal niche, which contribute to the well-
as a Reservoir of Microbiota
being of the host and can ward off or limit
and Enteric Pathogens
pathogenic invaders. It also illustrates, using
a few prominent and well-studied examples,
As we now know, the gastrointestinal tract of
humans and other vertebrates is one of the most
C. Josenhans (*) complex ecological niches imaginable. A multi-
Institute for Medical Microbiology and Hospital tude of different cells is combined to form the
Epidemiology, Hannover Medical School, Hannover, mucosal barrier and sample the molecules of var-
Germany
ious incoming compounds which can be both
DZIF, Partner Site Hannover-Braunschweig, living organisms, such as bacteria and parasites,
Braunschweig, Germany
or other intake, such as viruses, food and environ-
DZIF, Partner Site Munich, Munich, Germany mental particles. The intestinal tract is the largest
Max von Pettenkofer Institute, LMU Munich, Munich, body surface and an important entry portal but
Germany also harbors a major defense system against
e-mail: [email protected]
pathogens. The intestinal cell lining, the mucosa,
G. A. Grassl is characterized by a plethora of barrier functions
Institute for Medical Microbiology and Hospital
and defensive factors (Fig. 14.1). Intestinal bar-
Epidemiology, Hannover Medical School, Hannover,
Germany rier functions can be of physical, chemical, or
more complex, e.g., immunological nature. Phys-
DZIF, Partner Site Hannover-Braunschweig,
Braunschweig, Germany ical factors consist of the tight connection
e-mail: [email protected] between the cells of the mucosa and the overlying
# Springer International Publishing AG, part of Springer Nature 2018 209

D. Haller (ed.), The Gut Microbiome in Health and Disease,
https://doi.org/10.1007/978-3-319-90545-7_14
210 C. Josenhans and G. A. Grassl
Immune evasion, Adherence and secretion of toxins Mucus invasion, Motility

breaching barrier metal and nutrient acquisition, competition factors by Cell invasion / Transcytosis
Campylobacter, Salmonella Salmonella, E. coli, Campylobacter, T3SS, T4SS and T6SS Listeria, Salmonella, Bacteroides
ETBF Salmonella, E. coli, Campylobacter ETBF, Campylobacter
Barrier, mucus, pH, immune responses, scarcity of metals and nutrients, redox stress, other microbes
Pathogenic bacteria
enter mucus layer Intestinal lumen
Use metabolites and glycans from
host and microbiota
Mucus layer
E-cadherin
NF-KB cleavage Breach integrity of M Cell
epithelial barrier
Cell death (pyroptosis,
ß-catenin necroptosis,
apoptosis)
IECs
Transcription of c-Myc
cytoskeleton
Secretion of Proliferation immune response
B Cells barrier function
cytokines of IECs
Follicle
Legend DCs
Tight junction T Cells
PRR (TLR, NLR) APCs
Peyer‘s patch
Antimicrobial peptides
Secrotory IgA Lamina propria
Metabolites
Glycans (host, bacteria)
Fig. 14.1 Schematic overview of the intestinal niche, pathogens. The stimulation of PRRs by pathogens and
including its main components: the resident microbiota, commensal bacteria leads to the activation of NF-κB and
immune factors, and pathogenic bacteria. The intestinal production of pro-inflammatory cytokines, which are nec-
mucosa has numerous factors which shape the interaction essary for a healthy balance of responses (homeostasis) but
with nonpathogenic and pathogenic agents and incoming also for defense against pathogens. The hallmarks of
components of food and the environment. Mucus and detailed interactions of certain types of pathogens are
immune factors shape the microbiota and defend against included in the boxes above the schematic illustration
mucus layer. The mucus forms a netlike structure Hansson 2016). The outer mucus layer of healthy
of various glycans, glycoproteins, and mammals is easier to invade than the inner, dense
glycopeptides, the mucins (Bansil and Turner layer and harbors a complex community of
2017; Arike and Hansson 2016), which are pro- microbes, in particular bacteria (Johansson et al.
duced by specialized cells of the mucosa, the 2013). These bacteria are termed the commensal
goblet cells (Birchenough et al. 2015; Johansson microbiota. In recent years, significant advances
and Hansson 2016). The mucus consists of an have been made toward identifying the
inner layer, which is a very densely knit gel-like components of the commensal microbiota in
matrix and usually free of microbes, and an outer detail. This major advance is primarily due to
layer which is a gel of larger pore size and loos- improved techniques such as deep sequencing
ened structure (Johansson et al. 2013; Hansson which circumvent bacterial culture (Morgan and
2012). The chemical defense system in the intes- Huttenhower 2014; Hiergeist et al. 2016) but also
tine includes a rather low pH, lytic enzymes (e.g., to considerable success in cultivating numerous
proteases, lysozyme), and secreted defensive hitherto unculturable bacteria, ushering in a new
factors produced by cells of the mucosa (Jäger era of microaerophilic and anaerobic
et al. 2013; Sperandio et al. 2015; Johansson and “culturomics” (Lagier et al. 2012; Lagkouvardos
14 Microbiome and Diseases: Pathogen Infection 211
et al. 2016; Browne 2016). The microbiota and also as communities (Lagkouvardos et al.
appears to be specific for any given host species 2016) (for details of the Human Microbiome Proj-
(Ley et al. 2008; Chung et al. 2012; Eren et al. ect, see https://hmpdacc.org/). Time will tell
2015; Goodrich et al. 2016a; Clavel et al. 2017) whether these artificial/synthetic communities
and are not naturally transferred between humans remain stable in the autochthonous host or upon
and other mammals, although the dominant phyla heterologous transfer in vivo and can be stably
of the intestinal tract overlap between different propagated outside of their original host or, con-
vertebrate or mammalian hosts: Bacteroidetes sidered more likely, whether these consortia will
and Firmicutes are the main phyla represented in quickly degrade and evolve away from their origi-
the intestinal tract (Arumugam et al. 2011; nal composition over time.
Yatsunenko et al. 2012; Sankar et al. 2015; We are still missing information about certain
Hildebrand et al. 2013). In particular the intestinal microbiome components and their inter-
Clostridiales order within the Firmicutes and its play, not only on the wealth of bacteria in it but
families Lachnospiraceae, Ruminococcaceae, also on fungi, parasites, and viruses (Ursell et al.
and Clostridiaceae are important taxonomic 2012; Minot et al. 2013). Microbiome and viruses
groups, comprising many and diverse bacterial (the “virome”) crosstalk with each other, and it is
species in the intestinal niche. These taxa contain an important research goal to investigate in each
both pathogenic (Clostridium difficile) and case more closely, whether the interference is
numerous beneficial species (Buffie et al. 2015; beneficial for the host or any intestinal pathogen
Kim et al. 2017; Geva-Zatorsky et al. 2017). and in which context (see recent review by
What is a healthy human microbiota, and how Robinson and Pfeiffer 2014). Although not the
many species are contained in it? We cannot focus of this chapter, it is worthwhile mentioning
unambiguously answer this question yet; how- that frequent intestinal pathogenic viruses such as
ever, species estimates have become more precise rotavirus or norovirus also influence the host’s
and range from 100 to 500 species (Yatsunenko immune status and can partially recapitulate the
et al. 2012; Ursell et al. 2012; Thursby and Juge beneficial impact of bacterial microbiota
2017). The individual variation in microbiota components on diverse immune functions in
composition between persons is quite high. microbiota depletion models, an effect which is
Microbiota can be inherited from family probably triggered via innate recognition and type
members, in particular parents, grandparents, I interferon signaling (Kernbauer et al. 2014).
and other caretakers in the community. Individual Although the concept is still under debate,
genetic outfit plays a role in maintaining a certain different “enterotypes,” referring to the groupings
adapted and transmitted microbiota (Goodrich of distinct microbiota community types of differ-
et al. 2014). This has been underscored in ent host subgroups, have been described in
human twin studies and various animal humans and also in mice. The existence of
experiments (Lim et al. 2014; Goodrich et al. enterotypes may be dependent on genetic
2016b; Nguyen et al. 2015). The microbiota differences between different human individuals
matures naturally in a specific manner over the and also on environmental factors (Arumugam
course of a lifetime. Drastic changes in the et al. 2011; Hildebrand et al. 2013; Knights
microbiota composition and diversity occur in et al. 2014; Lim et al. 2014; Yin et al. 2017;
particular in the newborn and infants after Gibson et al. 2016; Costea et al. 2018).
weaning (Koenig et al. 2011) and may be, tran- Metagenomic approaches (16S rRNA gene
siently or permanently, influenced over time by amplicon sequencing and more comprehensive
environmental triggers (see last paragraphs of this methods capturing the complete intestinal
chapter). metagenome) on the basis of advanced high-
Many of the cultured intestinal bacteria (human, throughput sequencing technologies have helped
mouse) have been recently deposited in culture to dissect the functional and taxonomic diversity
collections and databases, both as single organisms in the culturable and non-culturable intestinal
microbiome (Qin et al. 2010; Sankar et al. 2015). PRR such as the Toll-like receptors (TLR)
Representation of functions and activities within (Iwasaki and Medzhitov 2015; Thaiss et al.
an individual microbiome is highly redundant, 2016).
which is independent of the presence of individ- Another striking trait of the intestinal niche is
ual taxa. This might ensure that different complex its richness and variable provisioning of various
microbiota types and their components are at least secondary metabolites, short-chain fatty acids
partially exchangeable for similar functionality (SCFA; Morrison and Preston 2016), glycans,
(Geva-Zatorsky et al. 2017). Functions of peptides, and electron acceptors. This variability
microbiota are manifold and consist of catabolic of resources for resident microbiota and
and anabolic properties (degradation of proteins pathogens alike is provided by variable “input,”
and complex glycans from food components, also that is, incoming dietary components, and subse-
associated with nutrient acquisition and, context- quently by varying metabolic properties of the
dependently, with induction of obesity), bile acid resident microbiota, which lead to a variable “out-
recycling and transformation, and provisioning of put” in residual metabolites. Moreover, inflam-
vitamins and essential amino acids (Blaut and matory bouts or infections can also lead to a
Clavel 2007; Le Chatelier et al. 2013). In addi- variation in these metabolic activities and output
tion, one major function of the intestinal metabolites.
microbiota is the balancing of innate and adaptive The intestinal niche characterized by the
intestinal immune functions [insight mainly gath- above-described, partially dynamic factors can
ered from germ-free rodent experiments; for be challenged by various niche-adapted, acute,
recent comprehensive reviews, see Macpherson and chronic pathogens, bacteria, viruses, eukary-
and McCoy (2015), Palm et al. (2015)]. This otic parasites, and fungi. The microbiota forms a
balance should lead to a long-term stable immune strong barrier against acute and chronic
response and a homeostatic state of low inflam- infections, termed colonization resistance
mation in the uninfected intestinal tract, despite (CR) (Buffie and Pamer 2013) (see also Sect.
the presence of multiple microbial ligands able to 14.3 for details and examples). The different
stimulate the innate immune system by the liga- factors forming resistance phenotypes include
tion of pattern recognition receptors (PRR). All local metabolic resilience and innate and adaptive
components of the immune system are influenced immune maturation and homeostasis (Rakoff-
by the microbiota starting shortly after birth Nahoum et al. 2004; Macpherson and McCoy
(Pabst et al. 2016; Tan et al. 2016): B-cells, 2015; Ohno 2016), metabolic immunity (O’Neill
T-cells, immune cell differentiation, and et al. 2016; Próchnicki and Latz 2017; Buck et al.
innateand adaptive lymphocytes. The adaptive 2017), the balanced production of antimicrobial
immune system is stabilized via the microbiota peptides by the host (Zasloff 2002; Günther et al.
by forming specific broadly reactive IgA species 2016; Perez-Lopez et al. 2016), and the release of
and IgA-producing memory B-cells (Kubinak antibiotic-like compounds by the intestinal
and Round 2016; Planer et al. 2016; Pabst et al. microbiota (Donia et al. 2014; Donia and
2016; McCoy et al. 2017; Okai et al. 2017) which Fischbach 2015). This defensive role of the
have long-term beneficial effects on intestinal microbiota against invading pathogens such as
health, even after the induction of dysbiosis. Sim- S. enterica and C. jejuni has been impressively
ilar mechanisms hold true for the maturation and verified in various rodent infection models, where
development of T-cell responses, which are like- the microbiota has been artificially depleted, for
wise shaped by the microbiota even in the instance, by antibiotic treatment (Kaiser et al.
absence of pathogens (Lindner et al. 2015). The 2012; Ekmekciu et al. 2017), or in germ-free
above-cited studies and others have shown that animals which have been compared to conven-
commensal microbiota, in addition to pathogens, tionally raised ones for infection susceptibility
can activate both innate and adaptive immune (Yrios and Balish 1986; Brugiroux et al. 2016).
responses in the gut, for instance, by binding to On the other hand, it has been demonstrated
already but certainly merits to be further explored typhoid fever (S. Typhi and S. Paratyphi). Some
that specific intestinal pathogenic bacteria even NTS strains (e.g., S. Typhimurium sequence type
use the innate host response in the presence of ST313) (Ramachandran et al. 2017; Okoro et al.
other microbes to enhance their colonization 2012) can also cause invasive life-threatening
potential (Günther et al. 2016). disease (iNTS) especially when underlying
In the following paragraphs of this chapter, we comorbidities (malnutrition) or coinfections
will mainly focus on the well-studied pathogens (HIV) are present.
Salmonella and Campylobacter as examples to Intestinal pathogens have to temporarily out-
illustrate the manifold ways how the microbiota compete commensal bacteria in order to cause
and the host interact with intestinal pathogenic infection and disease. In addition to dedicated
bacteria. host interaction modules such as the pathogenic-
ity island-encoded type III secretion systems (van
der Heijden and Finlay 2012; Jennings et al.
14.2 Specific Pathogens 2017), Salmonella possesses several mechanisms
of the (Gastro)Intestinal Tract: to overcome the CR provided by the complex
Common Traits, Examples microbiota, which are partially based on specific
and Specific Properties metabolic traits.
in the Face of a Resident Early after ingestion of the bacteria with
Microbiota contaminated food and in the absence of inflam-
mation, Salmonella Typhimurium expresses a
Intestinal bacterial pathogens, which are the focus nickel-iron hydrogenase (hyb) in the intestinal
of this chapter, cause for the most part acute rather lumen which allows it to utilize molecular hydro-
than chronic infections. Acute pathogens com- gen (produced by commensals) and a fumarate
prise mostly strongly pro-inflammatory bacteria reductase ( frdA) to convert fumarate, a metabo-
such as different E. coli pathotypes, Salmonella lite released by certain members of the
enterica serovars (Grassl and Finlay 2008), Shi- microbiota, to succinate. Succinate is an excellent
gella, Yersinia spp., other enterobacterial energy source for Salmonella which thus can
pathogens, Clostridium difficile, and Vibrio grow to high numbers in the intestinal lumen
cholerae. Among the fewer, more chronic, (Maier et al. 2013; Sassone-Corsi and Raffatellu
human pathogens are enterotoxigenic 2013). Free succinate in the intestine is also made
Bacteroides fragilis, some Campylobacter sp., as a fermentation product by commensal bacteria
and Listeria monocytogenes. Under certain such as Bacteroides thetaiotaomicron. However,
circumstances such as severe dysbiosis after anti- other commensals use succinate as an energy
biotic treatment, Clostridium difficile in the pres- source, and therefore, in a gut colonized with a
ence of its toxin can act as an acute severe complex microbiota, succinate levels in the intes-
pathogen, while it does not normally infect or tinal lumen are normally low. However, upon
multiply in the intestinal tract under microbiota- disturbance of the microbiota, for example, by
replete conditions. antibiotic treatment or upon inflammation, succi-
nate levels are elevated. It was recently shown
that succinate is taken up by Salmonella and
14.2.1 Metabolic Competition enters the tricarboxylic acid (TCA) cycle so that
of Pathogens with Commensal Salmonella expand and outcompete commensal
Bacteria (Fig. 14.2) strains (Spiga et al. 2017).
After expansion in the gut lumen, Salmonella
Salmonella enterica serovars can cause gastroin- travels through the mucus to the epithelium to
testinal disease (non-typhoidal Salmonella (NTS) invade the host tissue. Adhesion to and invasion
serovars such as S. Typhimurium or S. into host cells result in the production of
Enteritidis) or invasive, systemic disease or pro-inflammatory cytokines, chemoattraction of
H2 Salmonella
hyb hydrogenase
fumarate
succinate
anaerobic respiration
nitrate tetrathionate SPI-1

salmochelin
commensal
siderophores
Fe 3+ RNS ROS ethanolamine
thiosulfate H2S
lipocalin
Fig. 14.2 This figure illustrates the metabolic interplay cells produce lipocalin-2 which sequesters siderophores
between commensal bacteria and the intestinal pathogen from commensal bacteria, thereby limiting their access to
Salmonella as one example of interaction between the iron. However, Salmonella’s siderophore salmochelin
host, the microbiota, and a pathogen. Pathogens, as does cannot be bound by lipocalin-2 giving Salmonella priority
the commensal microbiota, need nutrients, and their niche access to iron. During inflammation, Salmonella also
adaptation is geared toward the acquisition of those from triggers the production of reactive oxygen species (ROS)
all components of the niche. In the anaerobic environment and reactive nitrogen species (RNS) leading to the forma-
of the intestinal lumen, Salmonella uses nickel-iron tion of alternative electron acceptors for Salmonella.
hydrogenase (hyb) to utilize molecular hydrogen, SPI-1—Salmonella pathogenicity island-1
providing energy for Salmonella to multiply. The host
immune cells, and pathological tissue change. circumvents these host defense mechanisms and
Salmonella-induced inflammation is outcompetes commensal bacteria by producing a
characterized by the destruction of tight junctions modified siderophore termed salmochelin that
between epithelial cells and the influx of cannot be bound by lipocalin-2 (Raffatellu et al.
leukocytes (neutrophils, macrophages, and den- 2009) and by expressing a high-affinity Zn2+
dritic cells) and lymphocytes and destruction of transporter (Liu et al. 2012).
the normal gut wall architecture. Another host defense against intracellular bac-
The metal ions iron and zinc are essential teria is the production of reactive nitrogen
micronutrients for bacteria. During inflammation, intermediates (RNI) and reactive oxygen
host cells (mainly neutrophils) produce large intermediates (ROI). Yet again, Salmonella has
amounts of lipocalin-2 which is able to sequester developed countermeasures to take advantage of
bacterial siderophores (iron carrier molecules) these defenses: A fraction of Salmonella bacteria
bound to iron. In addition, host cells secrete reside intracellularly in the so-called Salmonella-
calprotectin to sequester free zinc (Behnsen containing vacuole (SCV) where they are
et al. 2014). Thereby the host restricts access to protected from RNIs and ROIs. Furthermore, Sal-
these metal ions for bacteria. Salmonella monella can utilize metabolites made downstream
of reactive intermediates for respiration or its own layers can serve as carbon and energy sources
nutrition: for instance, reactive oxygen species and also as adhesion factors for bacteria (Tailford
can oxidize thiosulfate (a host metabolite derived et al. 2015; Ringot-Destrez et al. 2017; Juge
from commensal-produced H2S) to tetrathionate 2012). In addition, the glycosylation patterns on
which is used by Salmonella as an electron accep- intestinal epithelial cells and in the mucus can
tor for anaerobic respiration (Winter et al. 2010; influence microbiota composition and thus mod-
Winter and Bäumler 2011). Under these ulate the host’s susceptibility to infection and
circumstances, Salmonella can also use host- inflammation.
derived ethanolamine and microbiota-derived In order to invade and manipulate host cells,
1,2-propanediol as carbon sources (Price-Carter Salmonella has to get into close contact to the
et al. 2001; Thiennimitr et al. 2011; Faber et al. cells. For adhesion to mammalian cells or to the
2017). Similarly, a by-product of RNI metabo- mucus, the bacteria use various extensions such
lism in the presence of microbiota is nitrate (NO3) as flagella, fimbriae, and pili, most of which bind
which can also be used by Salmonella for anaero- to sugar residues on host glycoproteins or
bic respiration (Lopez et al. 2012). glycolipids. Enteric pathogens provide several
excellent examples how bacteria can bind to ter-
minal sugar residues on complex glycans. For
14.2.2 The Role of Intestinal Glycans example, Salmonella and other Enterobac-
in the Interplay Between teriaceae express type I fimbriae which bind to
Microbiota, Host mannosylated glycans. In addition, Salmonella
and Pathogens (Fig. 14.3) binds to fucose via StdA fimbriae (Chessa et al.
2009) and to GlcNAc and sialic acid via the
Glycans are abundant in the intestinal tract and adhesin SiiE (Gerlach et al. 2007; Wagner et al.
shape the interplay between resident microbiota, 2014).
the host, and incoming pathogens. Both the epi- While some commensal bacteria can degrade
thelial surface and the mucus layers are heavily complex glycans into shorter-chain sugars, many
glycosylated. About 80% of the total mucus mass other commensal and most pathogenic bacteria
is due to (O-linked) glycosylation. In contrast, the can only utilize mono- or disaccharides. For
epithelial glycocalyx consists of mostly N-linked example, the commensal Bacteroides sp. can
glycoproteins and glycolipids. While there is only hydrolyze complex glycans and take up and
a single mucus layer in the small intestine, the metabolize liberated sugars, while Salmonella
large intestine is covered by an inner, dense utilizes microbiota-derived free fucose and sialic
mucus layer which is normally devoid of bacteria, acid (Ng et al. 2013).
followed by an outer loose mucus layer which is Histo-blood group antigens are widely
heavily colonized by commensals (Johansson expressed by the intestinal epithelium. Intestinal
et al. 2011; Ermund et al. 2013). Mucus serves fucosylation (via fucosyltransferase (Fut)2) was
as a barrier to protect the epithelium from luminal shown to have a major impact on host suscepti-
bacteria, pathogens, and commensals. However, bility to various infections. For example, Fut2
pathogens have ways to penetrate the mucus, deficiency protects from human Norovirus and
either by active movement through flagella or by Helicobacter pylori infections but increases the
targeting M cells (specialized epithelial cells that risk for developing Crohn’s disease (Lindesmith
are located in the follicle-associated epithelium et al. 2003; Azevedo et al. 2008; McGovern et al.
overlying Peyer’s patches, which are not covered 2010). While fut2 is constitutively expressed in
by a thick mucus layer). In addition, some the large intestine, it is inducible by bacterial
pathogen-produced toxins can damage epithelial products in the ileum (Fig. 14.2) (Pickard et al.
cells so that less mucus is produced (McGuckin 2014): pathogens and commensals induce IL-23
et al. 2011). Apart from their barrier role, the production in dendritic cells (DCs) in the lamina
glycosylated mucins that make up the mucus propria, and IL-23 then induces IL-22 production
(CD toxin) B. fragilis (ETBF; BFT fragilysin)

antibiotics
dysbiosis dysbiosis
cell death necrosis, lesions, loss of barrier function

colon cancer
Fig. 14.3 One possibility to enhance pathogen survival in Clostridium toxins induces cell death and increased inflam-
the gut are bacterial toxins, as illustrated in this figure. Toxin- mation. B. fragilis toxin (BFT) cleaves E-cadherin and
mediated effects by the bacterial pathogens C. difficile and thereby destroys tight junctions, resulting in a leaky mucosal
enterotoxigenic B. fragilis are given as examples. Intensive barrier and inflammation. Toxin effects by enteropathogens
antibiotic treatment leads to the expansion of C. difficile, may ultimately contribute to tumorigenesis. ETBF—entero-
since the microbiota is severely depleted. Secretion of toxigenic B. fragilis
in ILC-3 cells. Finally, ILC-3-derived IL-22 (Rausch et al. 2015; Staubach et al. 2012). Other
triggers fut2 and antimicrobial peptide (AMP) histo-blood group antigens serve as receptors for
expression by epithelial cells (Goto et al. 2014). adhesion of other intestinal pathogens; e.g., Shiga
Intestinal epithelial fucosylation can block Sal- toxin-producing E. coli binds to H type I and
monella colonization (early after infection). How- sulfated H type II blood group antigens via its
ever, how exactly epithelial fucosylation blocks F18 fimbriae (Moonens et al. 2012; Coddens et al.
Salmonella infection remains unclear (Goto et al. 2009). Campylobacter binds terminal fucose on
2016). Others have shown that Salmonella H antigen (Ruiz-Palacios et al. 2003) (see also
possesses fimbriae that can bind to fucose below).
(Chessa et al. 2009) and Salmonella can effi- Inflammation helps Salmonella to access
ciently use fucose as a carbon and energy source glycans as energy sources. For example, during
(Ng et al. 2013). One mechanism how fucose can inflammation, motility allows Salmonella and
block a pathogen was demonstrated for another other intestinal pathogens such as Campylobacter
pathogen, enterohemorrhagic E. coli (EHEC): sp. to access inflammation-induced mucin
commensal-liberated L-fucose inhibits EHEC vir- components (Stecher et al. 2008). Antibiotic treat-
ulence gene expression (Pacheco et al. 2012). ment leads to an increase in oxidized sugar
Another intestinal blood group-related products such as glucarate or galactarate. Salmo-
glycosyltransferase is b4galnt2 which adds an nella can utilize these compounds and expand in
N-acetylgalactosamine (GalNAc) as a terminal their presence (Faber et al. 2016).
sugar onto glycoproteins and glycolipids The enteric pathogens Campylobacter sp. of
(Dall’Olio et al. 2014). By modifying microbiota the Epsilonproteobacteria, represented by the
composition, b4galnt2-modified sugars increase species C. jejuni and C. coli, are less
the susceptibility to Salmonella infections pro-inflammatory in humans but share a similar
intestinal niche with Salmonella and seem to C. jejuni metabolism in vivo are short-chain
overlap in a few important characteristics with fatty acids (SCFA) such as propionate, butyrate,
the enteric salmonellae as well, which will be and acetate (Gripp et al. 2011; Molnár et al. 2015;
illustrated in the next paragraph. Awad et al. 2016; Cresci et al. 2017), as well as
First of all, the resident microbiota is being dipeptides (breakdown products of proteins by
strongly engaged to modulate the specific life- the microbiota) (Gripp et al. 2011; Vorwerk
style of Campylobacter, as it is for Salmonella. et al. 2014). Intestinal Campylobacter species
Intestinal Campylobacter species colonize pre- have been demonstrated to display various
dominantly the intestinal mucus and intestinal glycans on their surface and possess, which is
crypts such as those of the chicken cecum unique among bacteria, both active N- and
(Beery et al. 1988). In the chicken gut, they O-glycosylation gene clusters (Young et al.
cause no or rather mild symptoms (Humphrey 2002; Szymanski and Gaynor 2012). Glycans of
et al. 2014); however, they become acutely path- pathogens or chronic colonizers such as
ogenic and can cause severe symptoms when they campylobacters are frequently mimicking human
colonize the human bowel in the jejunum and glycans as is the case for sialic acids (Guerry et al.
colon (Young et al. 2007). Although C. jejuni 2000; Gilbert et al. 2002; Bax et al. 2011;
are effectively separated from the bulk of the Szymanski and Gaynor 2012). This kind of
microbiota by mucus and their mucus-invading “molecular mimicry” is used by campylobacters
motility, their metabolism seems to be similarly to become rather invisible to the host immune
well adjusted to the interplay between those system and may even act in a tolerogenic manner
pathogens, microbiota, and the host. Therefore, (Perdicchio et al. 2016). Some C. jejuni surface
the microbiota is an important modulator of Cam- glycans have been shown to bind various human
pylobacter infection. Although we would like to lectins (Kilcoyne et al. 2014; Stephenson et al.
focus here on Campylobacter as another impor- 2014; Lu et al. 2015; Phongsisay et al. 2015;
tant paradigm for pathogen-glycan interactions, it Turonova et al. 2016). A few reports describe
is worthwhile mentioning that Campylobacter are that Campylobacter glycans can functionally
also able to source their metabolism and respira- interact with human lectins, for instance, with
tory chain from various by-products/metabolites Siglec-10 (Stephenson et al. 2014) or Siglec-7
of a complex microbiota. One similar example as (Avril et al. 2006; Heikema et al. 2013), which
for the salmonellae (see above) includes the use can lead to an increase in tolerogenic IL-10
of microbiota-derived tetrathionate as an electron (Stephenson et al. 2014). Sialoadhesin was also
acceptor for anaerobic respiration, together with shown to bind to C. jejuni (Klaas et al. 2012). One
the substrate ethanolamine (Liu et al. 2013). The may speculate that some lectin interactions influ-
interplay between host, microbiota, and specific ence immune polarization and, under certain
pathogen is also illustrated by the fact that circumstances, also induce immunological toler-
C. jejuni is metabolically very malleable, proba- ance. However, more definitive data are required
bly not only to adjust to different hosts but also to to strengthen this hypothesis. Campylobacter
be able to adapt to different microbiota types, glycans can also bind to host glycans directly
fluctuations, and compositions. with a high affinity, without the need for lectin
The importance of sugars for the Campylobac- intermediaries on the host side or other protein
ter intestinal lifestyle is substantial, both on the adhesins on the bacterial side. This has been
bacterial and on the host side (Day et al. 2012; revealed using glycan arrays of Campylobacter
Szymanski and Gaynor 2012). In addition to spe- surface sugars (Day et al. 2013, 2015).
cific microbiota-derived glycans (mainly mono- Recently, two large transposon mutant studies
and disaccharides) (Gripp et al. 2011; Stahl et al. which have explored the viability of C. jejuni
2011; Wagley et al. 2014; Vorwerk et al. 2015), mutants in different environments have expanded
some of the metabolites that are most likely the range of established niche-adaptation factors
sourced from the microbiota and used for of intestinal campylobacters (Gao et al. 2017; de
Vries et al. 2017), which also include some of 2012; Phongsisay 2016). The Campylobacter
those described above. Concerning the role of mimicry of human sugars is also likely to contrib-
glycans, fucose uptake, and metabolism (Stahl ute to the detrimental paralytic disease Guillain-
et al. 2011; Muraoka and Zhang 2011), general Barré syndrome in humans, by inducing antibody
glycosylation pathway and capsule synthesis formation against human glycosphingolipids, for
were globally reported to be essential for mouse example, against the ganglioside GM1 (Godschalk
colonization (Gao et al. 2017). For chicken colo- et al. 2004; Bax et al. 2011; Phongsisay 2016;
nization, capsule biosynthesis, general glycosyla- Lardone et al. 2016) or di-sialylated ganglioside
tion, and several lipooligosaccharide (LOS) mimics (Stephenson et al. 2013). Very recently, it
glycosylation enzymes, but not flagellar glycosyl- has been shown that microbiota transplantation in
ation, were found to be required (de Vries et al. humans may increase the formation of
2017). Interestingly, metabolome analysis autoantibodies which induce such neurological
(isotopologue profiling) in one of these recent problems in the presence of Campylobacter
studies showed that C. jejuni is able to recycle (Brooks et al. 2017). Interestingly, St Charles and
glycans (mainly glucose and galactose) of its colleagues have reported that antibiotic treatment
outer shell derived from LOS and capsular poly- leading to dysbiosis can also exacerbate Guillain-
saccharide (CPS) surface glycans, probably Barré-like symptoms in a Campylobacter mouse
serving as a nutrient reservoir (Gao et al. 2017). model (St Charles et al. 2017; Esan et al. 2017). In
In the chicken gut, one main niche of chronic this respect, establishing markers for Campylobac-
intestinal Campylobacter sp. colonization, ter strains that are prone to expressing these
mucins seem to contain an abundance of alpha- glycans or inducing human autoantibodies in
1,2-fucose and sulfated O-glycans (Struwe et al. healthy or dysbiotic patients will be very important
2015), much more than human intestinal mucus. in the future to prevent these sequelae but has not
However, this composition in the human or been achieved yet. It will also be useful to better
chicken intestinal mucus may vary by the influ- understand the impact of host glycan alterations
ence of dietary factors, microbiota, or other during low- or high-level inflammation on the host
pathogens, which needs to be clarified. It is well interaction potential, metabolism, and pathogene-
known that specific intestinal terminal glycans sis of Campylobacter and other intestinal patho-
such as alpha-1,2-fucose represent one main genic bacteria.
adherence factor for intestinal campylobacters We expect that metabolism- and glycan-
(Day et al. 2009, 2013; Ruiz-Palacios et al. dependent pathogen-microbiota crosstalk may
2003). The differential expression of these be important for many other intestinal pathogens
glycans in different spatial regions of the intestine as well and deserves further intensive
appears to inhibit the adherence and survival of investigations. It is also anticipated that the dis-
C. jejuni much more in the lower versus the upper covery of novel intestinal pathogens or
intestine (Day et al. 2009; Struwe et al. 2015). pathobionts will be facilitated by the ongoing
The overall number of glycans correlated extensive efforts to clarify microbiota composi-
inversely with the density of C. jejuni in vivo, tion and its contributions to health and disease.
and the presence of sulfated glycans may explic-
itly be required for inhibitory activities (Struwe
et al. 2015). These environmentally abundant 14.2.3 Direct Competitive Behavior
glycan cues may also explain the propensity of in Pathogen-Microbiota
some strains to readily take up and metabolize Interaction via Type VI
host- and microbiota-derived fucose as a nutrient Secretion Systems
(Gripp et al. 2011; Stahl et al. 2011). Campylo-
bacter glycans influence colonization and host Commensals and pathogens in the intestinal tract
immune responses by lectin interactions (Iovine not only crosstalk with the host (Vogt et al. 2015)
et al. 2008; van Sorge et al. 2009; Jervis et al. but also effectively communicate with each other
(Lustri et al. 2017). One additional, interesting For instance, enterotoxigenic Escherichia coli
aspect of microbe-host and microbe-pathogen (ETEC) (Madhavan and Sakellaris 2015) or
interplay in the intestinal tract is the competitive some enterohemorrhagic-like E. coli (EHEC) pro-
behavior between different members of the gut duce various potent enterotoxins, including Shiga
microbiota. The competition for nutrients in the toxin (Stx). Interestingly, microbiota and diet-
intestine is thought to be high, which raises the mediated microbiota modulation impacted on
question of competitive behavior, in particular of EHEC colonization levels, Stx tissue binding,
closely related species. The mechanisms of com- and downstream toxin effects in an animal
petition can rely on different bacterial factors, the model (Zumbrun et al. 2013). Vibrio cholerae
most important being metabolic competition (see disease symptoms of watery diarrhea are largely
above for examples), bacteriophages (Mills et al. caused by cholera toxin, which is encoded by a
2013) and toxin-antitoxin systems. Type VI lysogenic bacteriophage (ctx Φphage). Likewise,
secretion systems (T6SS) are complex secretion the less-known pathogenic bacterium enterotoxi-
systems in the outer membrane of Gram-negative genic Bacteroides fragilis (ETBF) makes
bacteria (Cascales and Cambillau 2012) which B. fragilis toxin (BFT), and Clostridium difficile
have recently attracted substantial research produces clostridial toxins A and B. Some strains
activities. Apart from their effects on host cells, produce a binary toxin called C. difficile transfer-
they are frequently being used to transport toxins ase (CDT) (Cowardin et al. 2016; Gerding et al.
or other bactericidal effectors into other, mostly 2014) which appears to contribute independently
closely related, Campylobacter spp. bacterial to disease symptoms. C. jejuni, some intestinal
cells (Basler et al. 2013). Various intestinal bacte- pathogenic E. coli strains, and enterohepatic
rial species, pathogens and nonpathogens, includ- Helicobacter species produce a different toxin,
ing Vibrio, Pseudomonas, Salmonella, Shigella, cytolethal distending toxin (CDT), which
and Bacteroides ssp., express T6SS and partly possesses a DNA-degrading enzymatic activity
use them for competition against the microbiota (Faïs et al. 2016). These toxins damage epithelial
(Pukatzki et al. 2007; Ho et al. 2014; Cianfanelli cells and the tight junctions by yet largely
et al. 2016; Sana et al. 2016; Joshi et al. 2017; unknown mechanisms and deplete certain cell
Anderson et al. 2017; Allsopp et al. 2017). types. Destroying goblet cells leads to a loss of
Recently, a comprehensive overview study of the mucus production and mucosal barrier dysfunc-
content of T6SS-bearing microbes in the human tion. Various toxin effects result in a leaky
intestine and the influence of T6SS on human mucosa and make the underlying tissue accessible
microbiome composition in children and adults to the pathogens and commensal bacteria, thus
was performed (Verster et al. 2017). Although far increasing local inflammation and invasion. BFT
from delivering final conclusions, the article states destroys tight junctions between epithelial cells
that T6SS are enriched in the intestinal tract and and cleaves E-cadherin, causing barrier dysfunc-
have a substantial influence on the microbiota tion and colitis, and ultimately promotes
composition and that this influence seems particu- tumorigenesis (Sears 2009; Wu et al. 2009).
larly important during the intestinal microbiota C. difficile toxins A and B glycosylate Rho
maturation phase in children. proteins, thereby manipulating host cell cytoskel-
eton and compromising epithelial integrity. In
many intestinal infections in conjunction with
14.2.4 Toxin-Mediated Effects the resident microbiota, the full extent and
of Intestinal Pathogens mechanisms of these toxin effects are not yet
on the Host (Fig. 14.4) understood and will require more detailed
investigations. This set of open questions also
Some gut pathogens secrete toxins to manipulate concerns the potential effects of the toxins on
host cells in order to destroy the epithelial barrier components of the microbiota, which has not
and improve their colonization and transmission. been studied so far.
Salmonella Campylobacter (jejuni, coli)
protease resistance, mucus-invasive motility

cell adherence
fucose sialic acid 1,2 propanediol microbiota-derived glycan

Salmonella Campylobacter
nutrient use
fucose uptake glycan mimicry
complex glycans and binding (sialic acid, gangliosides) lectin binding
(siglecs)
- tolerance or
AMPs Fut2
Fut2
TNFα
IL-17 IFNβ
IL-22 IL-22BP
IL-23
Foxp3+Treg
Th17 (Th1, Th2)
ILC3 (variable polarization by Campylobacter glycans)
Fig. 14.4 Interaction between host glycans, the and commensal bacteria can trigger cytokine production by
microbiota, and pathogenic bacteria is one major factor to host immune cells in a direct and indirect manner, which, in
shape the complex interplay in the intestinal niche and to turn, can stimulate terminal fucosylation of epithelial
provide nutrients to the well-adapted inhabitants. Salmo- glycans. Those and the production of antimicrobial peptides
nella and Campylobacter are given as prominent examples were, on one hand, shown to block Salmonella expansion
of pathogenic bacteria which make use of the glycan-rich and contribute to host defense mechanisms. On the other
environment for their own proliferation. For instance, both hand, terminal fucoses can also be utilized as nutrients by
bacterial pathogens, Salmonella and Campylobacter, cannot the pathogens, in particular by Campylobacter. Further-
degrade complex glycans present in the mucus on their own. more, Campylobacter uses variable glycosylation of its
However, after cleavage of complex glycans by commensal envelope as molecular mimicry, hiding from the host’s
bacteria, various resulting simple sugars (monosaccharides immune system. For instance, lectin binding of Campylo-
and disaccharides) are readily taken up and metabolized by bacter can lead to the induction of immune tolerance by
the pathogens, serving as energy sources. The pathogens IL-10 production
activated by commensal bacteria or their products

14.3 CR Against Enteric Pathogens, such as flagellin and LPS to upregulate the pro-
Environmental Interference duction and release of AMPs and reactive oxygen
with CR and Intervention and nitrogen species, which can kill invading
Strategies When CR Fails bacteria.
Indirect mechanisms of CR include the com-
The first reports showing that a complex petition for the same nutrient niche, the metabolic
microbiota confers colonization resistance conversion of primary into secondary bile acids,
(CR) against intestinal pathogens, including the as well as the stimulation of the host immune
abovementioned species, date back to the 1950s system and of the epithelium to produce mucus
(Bohnhoff et al. 1954, 1964; Miller et al. 1954). and antimicrobial peptides. Bacteriocins as an
CR can be provided by several direct and indirect additional, direct mechanism are bacteria-
mechanisms. Direct mechanisms include the pro- produced active protein toxins with microbicidal
duction of antimicrobial substances, e.g., activity, and most bacteriocins directly target a
bacteriocins or microcins (Hegarty et al. 2016; narrow set of related bacteria (Cotter et al. 2013).
Sassone-Corsi et al. 2016), or direct killing via Harnessing the power of bacteriocins may lead to
T6SS (see above). Epithelial cells can be directly the development of a novel set of narrow-
spectrum antibiotics. Additional metabolites such several communities sufficient to confer resis-
as the microbiota-produced SCFA can suppress tance against intestinal infections with S.
virulence gene expression of pathogens, e.g., Typhimurium (Brugiroux et al. 2016) or
butyrate suppresses Salmonella SPI-1 gene C. difficile (Buffie et al. 2015; Lawley et al.
expression (Gantois et al. 2006). In addition, 2012) have been defined. These studies are open-
butyrate is also a major energy source for epithe- ing new ways to reconstitute the microbiome in
lial cells and thus constitutes an important factor several disease states with targeted interventions
supporting a healthy epithelial barrier. Last but by restoring the “missing” commensal strains.
not least, these secondary metabolites shape the Most likely, protective strains will vary
host immune status (Alvarez-Curto and Milligan depending on the patients’ genetics and their
2016) which is important for tissue homeostasis endogenous microbiota. A couple of excellent
and adequate defense against pathogens. These recent reviews highlight the role of the resident
factors and their impact on pathogen CR may microbiota for CR (Olsan et al. 2017; Lawley and
also be influenced by dietary components. Walker 2013; Stecher and Hardt 2011; Stecher
Antibiotic treatment is frequently a necessity et al. 2013; Yurist-Doutsch et al. 2014; Kim et al.
and however provides one important, although 2017; Buffie and Pamer 2013).
unintended, environmental interference mecha- Looking into the future, the term “precision
nism toward CR. Antibiotics, on one hand, serve engineering or editing of microbiome” has been
to deplete pathogens but in all cases also alter the coined as one arm of an individualized medicine
resident microbiota, even after only one or two approach and intervention strategy (Buffie et al.
courses. The changes inflicted by antibiotics on 2015), directly effective against pathogens or indi-
the microbiota may be pervasive and permanent rectly while modulating the immune response
(Buffie and Pamer 2013). In particular if (Montalban-Arques et al. 2015). Two very recent
administered in early childhood, several courses examples do not directly add microbes but modu-
of antibiotics are assumed to lead to an irrevers- late microbiota indirectly by different metabolites
ible loss of beneficial microbes (Cho et al. 2012; or ions: One example is the unintended effect by
Blaser 2016; Kim et al. 2017; Olsan et al. 2017). the frequent food additive trehalose on microbiota
This state which is accompanied by other general and C. difficile (Collins et al. 2018), and the second
changes in the body (metabolic, immunological) one is the intentional reduction (precision editing)
is termed dysbiosis. This reduction in numbers of Salmonella and other Enterobacteriaceae
and diversity of resident bacteria also reduces within the microbiota by tungstate to inhibit the
beneficial effects of CR and renders patients bacterial molybdenum enzymes involved in
more susceptible on the short or even long term inflammation-induced metabolism (Zhu et al.
for infections such as common acute diarrheal 2018). The approach of microbiota editing also
pathogens (Kampmann et al. 2016), but also for includes the prospect to develop single bacterial
C. difficile or Enterococcus faecalis infection. species which can be protective or may even be
Therapeutically, some of these infections can be used in a therapeutic manner against infectious and
efficiently addressed by restoring the complex noninfectious, dysbiosis-triggered diseases.
microbiota using fecal microbiota transplantation
(FMT) (see Chap. 20). However, transferring a
complex donor microbiota carries the risk for " Controversy
co-transferring other pathogens or non-infectious
disease states such as metabolic syndrome or 1. To what extent do host genetics or the
obesity (Baxter and Colville 2016). Therefore, microbiome, respectively, influence sus-
there is an urgent need to define which set of ceptibility to intestinal infections?
harmless commensal strains are required to pro- 2. What is the role of interaction between
vide effective resistance to a specific infection microbiome, virome, fungome, archaeome,
and can be utilized for successful and long-lasting and the host for bacterial/viral/fungal
beneficial intervention strategies. Recently, infections?
3. Can we define a universal core consortium

of microbes providing CR against all or spe- infectious agents, including pathogenic
cific pathogens? Can we single out specific bacteria and viruses.
microbes/bacteria with particularly benefi- 2. Restoring microbiota complexity can be
cial effects in certain disease states? used to treat infections and restore colo-
4. How can the host-specific contributions of nization resistance, providing novel
immune response and microbiota be bet- strategies of disease intervention
ter defined for disease outcome of host- 3. Intestinal pathogens use the presence of
specific pathogens? microbiota, in particular of microbiota-
5. Are there direct effects of known bacterial derived metabolites, to improve their
(entero)toxins on commensals? own nutrient acquisition and compete
6. How does bacterial and inter-kingdom with residents
communication within the gut microbiota 4. Sugars/glycans formed by the intestinal
work and how effective is it? tissues and influenced by microbiota,
diet, and inflammation are widely used
by pathogens as adhesins and nutrient
History resources.
1. Original description of intestinal

microbiota and their specific functions
(expanded in the 1980s); first descriptions
References
of intestinal bacteria even originate from
the end of the nineteenth century (Nuttal Allsopp, L. P., Wood, T. E., Howard, S. A., Maggiorelli,
and Thierfelder 1895). F., Nolan, L. M., Wettstadt, S., & Filloux, A. (2017).
2. Description of the essential role of RsmA and AmrZ orchestrate the assembly of all three
microbiota for intestinal and immune type VI secretion systems in Pseudomonas aeruginosa.
Proceedings of the National Academy of Sciences of
homeostasis (from 2000 to present). the United States of America, 114, 7707–7712.
3. The advent of “culturomics,” which means Alvarez-Curto, E., & Milligan, G. (2016). Metabolism
the increase of culturable microbiota meets immunity: The role of free fatty acid receptors
components/strains from human and animal in the immune system. Biochemical Pharmacology,
114, 3–13.
intestine (from 2010 to present). Anderson, M. C., Vonaesch, P., Saffarian, A., Marteyn,
4. Modern revival of the microbiota transplant B. S., & Sansonetti, P. J. (2017). Shigella sonnei
approaches in Clostridium difficile colitis encodes a functional T6SS used for interbacterial com-
and the strengthened concept, mainly petition and niche occupancy. Cell Host and Microbe,
21, 769–776.e3.
underscored by germ-free animal models, Arike, L., & Hansson, G. C. (2016). The densely
that the microbiota in itself, in particular the O-glycosylated MUC2 mucin protects the intestine
intestinal resident microbiota, constitute an and provides food for the commensal bacteria. Journal
essential organ of the human body and are of Molecular Biology, 428, 3221–3229.
Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D.,
involved in CR (2010 to present). Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J.,
Bruls, T., Batto, J.-M., et al. (2011). Enterotypes of the
human gut microbiome. Nature, 473, 174–180.
Avril, T., Wagner, E. R., Willison, H. J., & Crocker, P. R.
(2006). Sialic acid-binding immunoglobulin-like lectin
Highlights 7 mediates selective recognition of sialylated glycans
expressed on Campylobacter jejuni lipooligosac-
1. A complex microbiota confers (coloni- charides. Infection and Immunity, 74, 4133–4141.
zation) resistance to a variety of Awad, W. A., Dublecz, F., Hess, C., Dublecz, K., Khayal,
B., Aschenbach, J. R., & Hess, M. (2016). Campylo-
bacter jejuni colonization promotes the translocation of
Escherichia coli to extra-intestinal organs and disturbs Browne, H. (2016). Antibiotics, gut bugs and the young.
the short-chain fatty acids profiles in the chicken gut. Nature Reviews. Microbiology, 14, 336.
Poultry Science, 95, 2259–2265. Brugiroux, S., Beutler, M., Pfann, C., Garzetti, D.,
Azevedo, M., Eriksson, S., Mendes, N., Serpa, J., Ruscheweyh, H.-J., Ring, D., Diehl, M., Herp, S.,
Figueiredo, C., Resende, L. P., Ruvoën-Clouet, N., Lötscher, Y., Hussain, S., et al. (2016). Genome-
Haas, R., Borén, T., Le Pendu, J., et al. (2008). Infec- guided design of a defined mouse microbiota that
tion by Helicobacter pylori expressing the BabA confers colonization resistance against Salmonella
adhesin is influenced by the secretor phenotype. The enterica serovar Typhimurium. Nature Microbiology,
Journal of Pathology, 215, 308–316. 2, 16215.
Bansil, R., & Turner, B. S. (2017). The biology of mucus: Buck, M. D., Sowell, R. T., Kaech, S. M., & Pearce, E. L.
Composition, synthesis and organization. Advanced (2017). Metabolic instruction of immunity. Cell, 169,
Drug Delivery Reviews, 124, 3–15. 570–586.
Basler, M., Ho, B. T., & Mekalanos, J. J. (2013). Tit-for- Buffie, C. G., & Pamer, E. G. (2013). Microbiota-mediated
tat: Type VI secretion system counterattack during colonization resistance against intestinal pathogens.
bacterial cell-cell interactions. Cell, 152, 884–894. Nature Reviews. Immunology, 13, 790–801.
Bax, M., Kuijf, M. L., Heikema, A. P., van Rijs, W., Buffie, C. G., Bucci, V., Stein, R. R., McKenney, P. T.,
Bruijns, S. C. M., García-Vallejo, J. J., Crocker, Ling, L., Gobourne, A., No, D., Liu, H., Kinnebrew,
P. R., Jacobs, B. C., van Vliet, S. J., & van Kooyk, M., Viale, A., et al. (2015). Precision microbiome
Y. (2011). Campylobacter jejuni lipooligosaccharides reconstitution restores bile acid mediated resistance to
modulate dendritic cell-mediated T cell polarization in Clostridium difficile. Nature, 517, 205–208.
a sialic acid linkage-dependent manner. Infection and Cascales, E., & Cambillau, C. (2012). Structural biology
Immunity, 79, 2681–2689. of type VI secretion systems. Philosophical
Baxter, M., & Colville, A. (2016). Adverse events in faecal Transactions of the Royal Society of London.
microbiota transplant: A review of the literature. The Series B, Biological Sciences, 367, 1102–1111.
Journal of Hospital Infection, 92, 117–127. Chessa, D., Winter, M. G., Jakomin, M., & Baumler, A. J.
Beery, J. T., Hugdahl, M. B., & Doyle, M. P. (1988). (2009). Salmonella enterica serotype Typhimurium Std
Colonization of gastrointestinal tracts of chicks by fimbriae bind terminal alpha(1,2)fucose residues in the
Campylobacter jejuni. Applied and Environmental cecal mucosa. Molecular Microbiology, 71, 864–875.
Microbiology, 54, 2365–2370. Cho, I., Yamanishi, S., Cox, L., Methé, B. A., Zavadil, J.,
Behnsen, J., Jellbauer, S., Wong, C. P., Edwards, R. A., Li, K., Gao, Z., Mahana, D., Raju, K., Teitler, I., et al.
George, M. D., Ouyang, W., & Raffatellu, M. (2014). (2012). Antibiotics in early life alter the murine colonic
The cytokine IL-22 promotes pathogen colonization by microbiome and adiposity. Nature, 488, 621–626.
suppressing related commensal bacteria. Immunity, 40, Chung, H., Pamp, S. J., Hill, J. A., Surana, N. K.,
262–273. Edelman, S. M., Troy, E. B., Reading, N. C.,
Birchenough, G. M. H., Johansson, M. E. V., Gustafsson, Villablanca, E. J., Wang, S., Mora, J. R., et al.
J. K., Bergström, J. H., & Hansson, G. C. (2015). New (2012). Gut immune maturation depends on coloniza-
developments in goblet cell mucus secretion and function with a host-specific microbiota. Cell, 149,
tion. Mucosal Immunology, 8, 712–719. 1578–1593.
Blaser, M. J. (2016). Antibiotic use and its consequences Cianfanelli, F. R., Monlezun, L., & Coulthurst, S. J.
for the normal microbiome. Science, 352, 544–545. (2016). Aim, load, fire: The type VI secretion system,
Blaut, M., & Clavel, T. (2007). Metabolic diversity of the a bacterial nanoweapon. Trends in Microbiology, 24,
intestinal microbiota: Implications for health and dis- 51–62.
ease. The Journal of Nutrition, 137, 751S–755S. Clavel, T., Lagkouvardos, I., & Stecher, B. (2017). From
Bohnhoff, M., Drake, B. L., & Miller, C. P. (1954). Effect complex gut communities to minimal microbiomes via
of streptomycin on susceptibility of intestinal tract to cultivation. Current Opinion in Microbiology, 38,
experimental Salmonella infection. Proceedings of the 148–155.
Society for Experimental Biology and Medicine, 86, Coddens, A., Diswall, M., Angström, J., Breimer, M. E.,
132–137. Goddeeris, B., Cox, E., & Teneberg, S. (2009). Recog-
Bohnhoff, M., Miller, C. P., & Martin, W. R. (1964). nition of blood group ABH type 1 determinants by the
Resistance of the mouse’s intestinal tract to experimen- FedF adhesin of F18-fimbriated Escherichia coli. The
tal Salmonella infection. I. Factors which interfere with Journal of Biological Chemistry, 284, 9713–9726.
the initiation of infection by oral inoculation. The Collins, J., Robinson, C., Danhof, H., Knetsch, C. W., van
Journal of Experimental Medicine, 120, 805–816. Leeuwen, H. C., Lawley, T. D., Auchtung, J. M., &
Brooks, P. T., Brakel, K. A., Bell, J. A., Bejcek, C. E., Britton, R. A. (2018). Dietary trehalose enhances viru-
Gilpin, T., Brudvig, J. M., & Mansfield, L. S. (2017). lence of epidemic Clostridium difficile. Nature, 553,
Transplanted human fecal microbiota enhanced 291–294.
Guillain Barré syndrome autoantibody responses after Costea, P. I., Hildebrand, F., Manimozhiyan, A., Bäckhed,
Campylobacter jejuni infection in C57BL/6 mice. F., Blaser, M. J., Bushman, F. D., de Vos, W. M.,
Microbiome, 5, 92. Ehrlich, S. D., Fraser, C. M., Hattori, M., et al.
(2018). Enterotypes in the landscape of gut microbial Ekmekciu, I., von Klitzing, E., Fiebiger, U., Escher, U.,
community composition. Nature Microbiology, 3, Neumann, C., Bacher, P., Scheffold, A., Kühl, A. A.,
8–16. Bereswill, S., & Heimesaat, M. M. (2017). Immune
Cotter, P. D., Ross, R. P., & Hill, C. (2013). Bacteriocins – responses to broad-spectrum antibiotic treatment and
a viable alternative to antibiotics? Nature Reviews. fecal microbiota transplantation in mice. Frontiers in
Microbiology, 11, 95–105. Immunology, 8, 397.
Cowardin, C. A., Buonomo, E. L., Saleh, M. M., Wilson, Eren, A. M., Morrison, H. G., Lescault, P. J., Reveillaud,
M. G., Burgess, S. L., Kuehne, S. A., Schwan, C., J., Vineis, J. H., & Sogin, M. L. (2015). Minimum
Eichhoff, A. M., Koch-Nolte, F., Lyras, D., et al. entropy decomposition: Unsupervised oligotyping for
(2016). The binary toxin CDT enhances Clostridium sensitive partitioning of high-throughput marker gene
difficile virulence by suppressing protective colonic sequences. The ISME Journal, 9, 968–979.
eosinophilia. Nature Microbiology, 1, 16108. Ermund, A., Schütte, A., Johansson, M. E. V., Gustafsson,
Cresci, G. A. M., Mayor, P. C., & Thompson, S. A. J. K., & Hansson, G. C. (2013). Studies of mucus in
(2017). Effect of butyrate and Lactobacillus GG on a mouse stomach, small intestine, and colon.
butyrate receptor and transporter during Campylobac- I. Gastrointestinal mucus layers have different
ter jejuni exposure. FEMS Microbiology Letters, 364. properties depending on location as well as over the
https://doi.org/10.1093/femsle/fnx046. Peyer’s patches. American Journal of Physiology. Gas-
Dall’Olio, F., Malagolini, N., Chiricolo, M., Trinchera, trointestinal and Liver Physiology, 305, G341–G347.
M., & Harduin-Lepers, A. (2014). The expanding Esan, O. B., Pearce, M., van Hecke, O., Roberts, N.,
roles of the Sd(a)/Cad carbohydrate antigen and its Collins, D. R. J., Violato, M., McCarthy, N., Perera,
cognate glycosyltransferase B4GALNT2. Biochimica R., & Fanshawe, T. R. (2017). Factors associated with
et Biophysica Acta, 1840, 443–453. sequelae of Campylobacter and non-typhoidal Salmo-
Day, C. J., Tiralongo, J., Hartnell, R. D., Logue, C.-A., nella infections: A systematic review. EBio Medicine,
Wilson, J. C., von Itzstein, M., & Korolik, V. (2009). 15, 100–111.
Differential carbohydrate recognition by Campylobac- Faber, F., Tran, L., Byndloss, M. X., Lopez, C. A.,
ter jejuni strain 11168: Influences of temperature and Velazquez, E. M., Kerrinnes, T., Nuccio, S.-P.,
growth conditions. PLoS One, 4, e4927. Wangdi, T., Fiehn, O., Tsolis, R. M., et al. (2016).
Day, C. J., Semchenko, E. A., & Korolik, V. (2012). Host-mediated sugar oxidation promotes post-
Glycoconjugates play a key role in Campylobacter antibiotic pathogen expansion. Nature, 534, 697–699.
jejuni infection: Interactions between host and pathogen. Faber, F., Thiennimitr, P., Spiga, L., Byndloss, M. X.,
Frontiers in Cellular and Infection Microbiology, 2, 9. Litvak, Y., Lawhon, S., Andrews-Polymenis, H. L.,
Day, C. J., Tram, G., Hartley-Tassell, L. E., Tiralongo, J., Winter, S. E., & Bäumler, A. J. (2017). Respiration
& Korolik, V. (2013). Assessment of glycan of microbiota-derived 1,2-propanediol drives Salmo-
interactions of clinical and avian isolates of Campylo- nella expansion during Colitis. PLoS Pathogens, 13,
bacter jejuni. BMC Microbiology, 13, 228. e1006129.
Day, C. J., Tran, E. N., Semchenko, E. A., Tram, G., Faïs, T., Delmas, J., Serres, A., Bonnet, R., & Dalmasso,
Hartley-Tassell, L. E., Ng, P. S. K., King, R. M., G. (2016). Impact of CDT toxin on human diseases.
Ulanovsky, R., McAtamney, S., Apicella, M. A., Toxins, 8. https://doi.org/10.3390/toxins8070220.
et al. (2015). Glycan:glycan interactions: High affinity Gantois, I., Ducatelle, R., Pasmans, F., Haesebrouck, F.,
biomolecular interactions that can mediate binding of Hautefort, I., Thompson, A., Hinton, J. C., & Van
pathogenic bacteria to host cells. Proceedings of the Immerseel, F. (2006). Butyrate specifically down-
National Academy of Sciences of the United States of regulates salmonella pathogenicity island 1 gene
America, 112, E7266–E7275. expression. Applied and Environmental Microbiology,
de Vries, S. P., Gupta, S., Baig, A., Wright, E., Wedley, 72, 946–949.
A., Jensen, A. N., Lora, L. L., Humphrey, S., Gao, B., Vorwerk, H., Huber, C., Lara-Tejero, M., Mohr,
Skovgard, H., Macleod, K., et al. (2017). Genome- J., Goodman, A. L., Eisenreich, W., Galán, J. E., &
wide fitness analyses of the foodborne pathogen Cam- Hofreuter, D. (2017). Metabolic and fitness
pylobacter jejuni in in vitro and in vivo models. Scien- determinants for in vitro growth and intestinal coloni-
tific Reports, 7, 1251. zation of the bacterial pathogen Campylobacter jejuni.
Donia, M. S., & Fischbach, M. A. (2015). HUMAN PLoS Biology, 15, e2001390.
MICROBIOTA. Small molecules from the human Gerding, D. N., Johnson, S., Rupnik, M., & Aktories,
microbiota. Science, 349, 1254766. K. (2014). Clostridium difficile binary toxin CDT:
Donia, M. S., Cimermancic, P., Schulze, C. J., Wieland Mechanism, epidemiology, and potential clinical
Brown, L. C., Martin, J., Mitreva, M., Clardy, J., importance. Gut Microbes, 5, 15–27.
Linington, R. G., & Fischbach, M. A. (2014). A sys- Gerlach, R. G., Jackel, D., Stecher, B., Wagner, C., Lupas,
tematic analysis of biosynthetic gene clusters in the A., Hardt, W. D., & Hensel, M. (2007). Salmonella
human microbiome reveals a common family of Pathogenicity Island 4 encodes a giant non-fimbrial
antibiotics. Cell, 158, 1402–1414. adhesin and the cognate type 1 secretion system. Cel-
lular Microbiology, 9, 1834–1850.
Geva-Zatorsky, N., Sefik, E., Kua, L., Pasman, L., Tan, Günther, C., Josenhans, C., & Wehkamp, J. (2016).
T. G., Ortiz-Lopez, A., Yanortsang, T. B., Yang, L., Crosstalk between microbiota, pathogens and the
Jupp, R., Mathis, D., et al. (2017). Mining the human innate immune responses. International Journal of
gut microbiota for immunomodulatory organisms. Medical Microbiology, 306, 257–265.
Cell, 168, 928–943.e11. Hansson, G. C. (2012). Role of mucus layers in gut infec-
Gibson, T. E., Bashan, A., Cao, H.-T., Weiss, S. T., & Liu, tion and inflammation. Current Opinion in Microbiol-
Y.-Y. (2016). On the origins and control of community ogy, 15, 57–62.
types in the human microbiome. PLoS Computational Hegarty, J. W., Guinane, C. M., Ross, R. P., Hill, C., &
Biology, 12, e1004688. Cotter, P. D. (2016). Bacteriocin production: A relatively
Gilbert, M., Karwaski, M.-F., Bernatchez, S., Young, unharnessed probiotic trait? F1000Research, 5, 2587.
N. M., Taboada, E., Michniewicz, J., Cunningham, Heikema, A. P., Jacobs, B. C., Horst-Kreft, D., Huizinga,
A.-M., & Wakarchuk, W. W. (2002). The genetic R., Kuijf, M. L., Endtz, H. P., Samsom, J. N., & van
bases for the variation in the lipo-oligosaccharide of Wamel, W. J. B. (2013). Siglec-7 specifically
the mucosal pathogen, Campylobacter jejuni. Biosyn- recognizes Campylobacter jejuni strains associated
thesis of sialylated ganglioside mimics in the core with oculomotor weakness in Guillain-Barré syndrome
oligosaccharide. The Journal of Biological Chemistry, and Miller Fisher syndrome. Clinical Microbiology
277, 327–337. and Infection, 19, E106–E112.
Godschalk, P. C. R., Heikema, A. P., Gilbert, M., Hiergeist, A., Reischl, U., Priority Program 1656 Intestinal
Komagamine, T., Ang, C. W., Glerum, J., Brochu, Microbiota Consortium/quality assessment
D., Li, J., Yuki, N., Jacobs, B. C., et al. (2004). The participants, & Gessner, A. (2016). Multicenter quality
crucial role of Campylobacter jejuni genes in anti- assessment of 16S ribosomal DNA-sequencing for
ganglioside antibody induction in Guillain-Barre syn- microbiome analyses reveals high inter-center
drome. The Journal of Clinical Investigation, 114, variability. International Journal of Medical Microbi-
1659–1665. ology, 306, 334–342.
Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Hildebrand, F., Nguyen, T. L. A., Brinkman, B., Yunta,
Koren, O., Blekhman, R., Beaumont, M., Van Treuren, R. G., Cauwe, B., Vandenabeele, P., Liston, A., &
W., Knight, R., Bell, J. T., et al. (2014). Human genet- Raes, J. (2013). Inflammation-associated enterotypes,
ics shape the gut microbiome. Cell, 159, 789–799. host genotype, cage and inter-individual effects drive
Goodrich, J. K., Davenport, E. R., Waters, J. L., Clark, gut microbiota variation in common laboratory mice.
A. G., & Ley, R. E. (2016a). Cross-species Genome Biology, 14, R4.
comparisons of host genetic associations with the Ho, B. T., Dong, T. G., & Mekalanos, J. J. (2014). A view
microbiome. Science, 352, 532–535. to a kill: The bacterial type VI secretion system. Cell
Goodrich, J. K., Davenport, E. R., Beaumont, M., Jackson, Host and Microbe, 15, 9–21.
M. A., Knight, R., Ober, C., Spector, T. D., Bell, J. T., Humphrey, S., Chaloner, G., Kemmett, K., Davidson, N.,
Clark, A. G., & Ley, R. E. (2016b). Genetic Williams, N., Kipar, A., Humphrey, T., & Wigley,
determinants of the gut microbiome in UK twins. Cell P. (2014). Campylobacter jejuni is not merely a com-
Host and Microbe, 19, 731–743. mensal in commercial broiler chickens and affects bird
Goto, Y., Obata, T., Kunisawa, J., Sato, S., Ivanov, I. I., welfare. MBio, 5, e01364-01314.
Lamichhane, A., Takeyama, N., Kamioka, M., Iovine, N. M., Pursnani, S., Voldman, A., Wasserman, G.,
Sakamoto, M., Matsuki, T., et al. (2014). Innate lym- Blaser, M. J., & Weinrauch, Y. (2008). Reactive nitro-
phoid cells regulate intestinal epithelial cell glycosyla- gen species contribute to innate host defense against
tion. Science, 345, 1254009. Campylobacter jejuni. Infection and Immunity, 76,
Goto, Y., Uematsu, S., & Kiyono, H. (2016). Epithelial 986–993.
glycosylation in gut homeostasis and inflammation. Iwasaki, A., & Medzhitov, R. (2015). Control of adaptive
Nature Immunology, 17, 1244–1251. immunity by the innate immune system. Nature Immu-
Grassl, G. A., & Finlay, B. B. (2008). Pathogenesis of nology, 16, 343–353.
enteric Salmonella infections. Current Opinion in Gas- Jäger, S., Stange, E. F., & Wehkamp, J. (2013). Inflamma-
troenterology, 24, 22–26. tory bowel disease: An impaired barrier disease.
Gripp, E., Hlahla, D., Didelot, X., Kops, F., Maurischat, Langenbeck’s Archives of Surgery, 398, 1–12.
S., Tedin, K., Alter, T., Ellerbroek, L., Schreiber, K., Jennings, E., Thurston, T. L. M., & Holden, D. W. (2017).
Schomburg, D., et al. (2011). Closely related Cam- Salmonella SPI-2 type III secretion system effectors:
pylobacter jejuni strains from different sources reveal Molecular mechanisms and physiological
a generalist rather than a specialist lifestyle. BMC consequences. Cell Host and Microbe, 22, 217–231.
Genomics, 12, 584. Jervis, A. J., Butler, J. A., Lawson, A. J., Langdon, R.,
Guerry, P., Ewing, C. P., Hickey, T. E., Prendergast, Wren, B. W., & Linton, D. (2012). Characterization of
M. M., & Moran, A. P. (2000). Sialylation of lipooligo- the structurally diverse N-linked glycans of Campylo-
saccharide cores affects immunogenicity and serum bacter species. Journal of Bacteriology, 194,
resistance of Campylobacter jejuni. Infection and 2355–2362.
Immunity, 68, 6656–6662.
Johansson, M. E. V., & Hansson, G. C. (2016). Immuno- Kubinak, J. L., & Round, J. L. (2016). Do antibodies select
logical aspects of intestinal mucus and mucins. Nature a healthy microbiota? Nature Reviews. Immunology,
Reviews. Immunology, 16, 639–649. 16, 767–774.
Johansson, M. E. V., Ambort, D., Pelaseyed, T., Schütte, Lagier, J.-C., Armougom, F., Million, M., Hugon, P.,
A., Gustafsson, J. K., Ermund, A., Subramani, D. B., Pagnier, I., Robert, C., Bittar, F., Fournous, G.,
Holmén-Larsson, J. M., Thomsson, K. A., Bergström, Gimenez, G., Maraninchi, M., et al. (2012). Microbial
J. H., et al. (2011). Composition and functional role of culturomics: Paradigm shift in the human gut
the mucus layers in the intestine. Cellular and Molecu- microbiome study. Clinical Microbiology and Infec-
lar Life Sciences, 68, 3635–3641. tion, 18, 1185–1193.
Johansson, M. E. V., Sjövall, H., & Hansson, G. C. (2013). Lagkouvardos, I., Pukall, R., Abt, B., Foesel, B. U., Meier-
The gastrointestinal mucus system in health and dis- Kolthoff, J. P., Kumar, N., Bresciani, A., Martínez, I.,
ease. Nature Reviews. Gastroenterology & Just, S., Ziegler, C., et al. (2016). The Mouse Intestinal
Hepatology, 10, 352–361. Bacterial Collection (miBC) provides host-specific
Joshi, A., Kostiuk, B., Rogers, A., Teschler, J., Pukatzki, insight into cultured diversity and functional potential
S., & Yildiz, F. H. (2017). Rules of engagement: The of the gut microbiota. Nature Microbiology, 1, 16131.
type VI secretion system in Vibrio cholerae. Trends in Lardone, R. D., Yuki, N., Irazoqui, F. J., & Nores, G. A.
Microbiology, 25, 267–279. (2016). Individual restriction of fine specificity
Juge, N. (2012). Microbial adhesins to gastrointestinal variability in anti-GM1 IgG antibodies associated
mucus. Trends in Microbiology, 20, 30–39. with Guillain-Barré syndrome. Scientific Reports, 6,
Kaiser, P., Diard, M., Stecher, B., & Hardt, W.-D. (2012). 19901.
The streptomycin mouse model for Salmonella diar- Lawley, T. D., & Walker, A. W. (2013). Intestinal coloni-
rhea: Functional analysis of the microbiota, the zation resistance. Immunology, 138, 1–11.
pathogen’s virulence factors, and the host’s mucosal Lawley, T. D., Clare, S., Walker, A. W., Stares, M. D.,
immune response. Immunological Reviews, 245, Connor, T. R., Raisen, C., Goulding, D., Rad, R.,
56–83. Schreiber, F., Brandt, C., et al. (2012). Targeted resto-
Kampmann, C., Dicksved, J., Engstrand, L., & Rautelin, ration of the intestinal microbiota with a simple,
H. (2016). Composition of human faecal microbiota in defined bacteriotherapy resolves relapsing Clostridium
resistance to Campylobacter infection. Clinical Micro- difficile disease in mice. PLoS Pathogens, 8,
biology and Infection, 22, 61–61. e1002995.
Kernbauer, E., Ding, Y., & Cadwell, K. (2014). An enteric Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand,
virus can replace the beneficial function of commensal F., Falony, G., Almeida, M., Arumugam, M., Batto, J.-
bacteria. Nature, 516, 94–98. M., Kennedy, S., et al. (2013). Richness of human gut
Kilcoyne, M., Twomey, M. E., Gerlach, J. Q., Kane, M., microbiome correlates with metabolic markers.
Moran, A. P., & Joshi, L. (2014). Campylobacter jejuni Nature, 500, 541–546.
strain discrimination and temperature-dependent Ley, R. E., Lozupone, C. A., Hamady, M., Knight, R., &
glycome expression profiling by lectin microarray. Gordon, J. I. (2008). Worlds within worlds: Evolution
Carbohydrate Research, 389, 123–133. of the vertebrate gut microbiota. Nature Reviews.
Kim, S., Covington, A., & Pamer, E. G. (2017). The Microbiology, 6, 776–788.
intestinal microbiota: Antibiotics, colonization resis- Lim, M. Y., Rho, M., Song, Y.-M., Lee, K., Sung, J., &
tance, and enteric pathogens. Immunological Reviews, Ko, G. (2014). Stability of gut enterotypes in Korean
279, 90–105. monozygotic twins and their association with
Klaas, M., Oetke, C., Lewis, L. E., Erwig, L. P., Heikema, biomarkers and diet. Scientific Reports, 4, 7348.
A. P., Easton, A., Willison, H. J., & Crocker, P. R. Lindesmith, L., Moe, C., Marionneau, S., Ruvoen, N., Jiang,
(2012). Sialoadhesin promotes rapid proinflammatory X., Lindblad, L., Stewart, P., LePendu, J., & Baric,
and type I IFN responses to a sialylated pathogen, R. (2003). Human susceptibility and resistance to
Campylobacter jejuni. Journal of Immunology Norwalk virus infection. Nature Medicine, 9, 548–553.
(Baltimore, MD), 1950(189), 2414–2422. Lindner, C., Thomsen, I., Wahl, B., Ugur, M., Sethi,
Knights, D., Ward, T. L., McKinlay, C. E., Miller, H., M. K., Friedrichsen, M., Smoczek, A., Ott, S.,
Gonzalez, A., McDonald, D., & Knight, R. (2014). Baumann, U., Suerbaum, S., et al. (2015). Diversifica-
Rethinking “enterotypes”. Cell Host and Microbe, 16, tion of memory B cells drives the continuous adapta-
433–437. tion of secretory antibodies to gut microbiota. Nature
Koenig, J. E., Spor, A., Scalfone, N., Fricker, A. D., Immunology, 16, 880–888.
Stombaugh, J., Knight, R., Angenent, L. T., & Ley, Liu, J. Z., Jellbauer, S., Poe, A. J., Ton, V., Pesciaroli, M.,
R. E. (2011). Succession of microbial consortia in the Kehl-Fie, T. E., Restrepo, N. A., Hosking, M. P.,
developing infant gut microbiome. Proceedings of the Edwards, R. A., Battistoni, A., et al. (2012). Zinc
National Academy of Sciences of the United States of sequestration by the neutrophil protein calprotectin
America, 108(Suppl 1), 4578–4585. enhances Salmonella growth in the inflamed gut. Cell
Host and Microbe, 11, 227–239.
Liu, Y. W., Denkmann, K., Kosciow, K., Dahl, C., & Campylobacter jejuni in broiler chickens. Journal of
Kelly, D. J. (2013). Tetrathionate stimulated growth Applied Microbiology, 118, 245–254.
of Campylobacter jejuni identifies a new type of Montalban-Arques, A., De Schryver, P., Bossier, P.,
bi-functional tetrathionate reductase (TsdA) that is Gorkiewicz, G., Mulero, V., Gatlin, D. M., &
widely distributed in bacteria. Molecular Microbiol- Galindo-Villegas, J. (2015). Selective manipulation of
ogy, 88, 173–188. the gut microbiota improves immune status in
Lopez, C. A., Winter, S. E., Rivera-Chavez, F., Xavier, vertebrates. Frontiers in Immunology, 6, 512.
M. N., Poon, V., Nuccio, S. P., Tsolis, R. M., & Moonens, K., Bouckaert, J., Coddens, A., Tran, T.,
Baumler, A. J. (2012). Phage-mediated acquisition of Panjikar, S., De Kerpel, M., Cox, E., Remaut, H., &
a type III secreted effector protein boosts growth of De Greve, H. (2012). Structural insight in histo-blood
salmonella by nitrate respiration. MBio, 3. https://doi. group binding by the F18 fimbrial adhesin FedF.
org/10.1128/mBio.00143-12. Molecular Microbiology, 86, 82–95.
Lu, Q., Li, S., & Shao, F. (2015). Sweet talk: Protein Morgan, X. C., & Huttenhower, C. (2014). Meta’omic
glycosylation in bacterial interaction with the host. analytic techniques for studying the intestinal
Trends in Microbiology, 23, 630–641. microbiome. Gastroenterology, 146, 1437–1448.e1.
Lustri, B. C., Sperandio, V., & Moreira, C. G. (2017). Morrison, D. J., & Preston, T. (2016). Formation of short
Bacterial chat: Intestinal metabolites and signals in chain fatty acids by the gut microbiota and their impact
host-microbiota-pathogen interactions. Infection and on human metabolism. Gut Microbes, 7, 189–200.
Immunity, 85. https://doi.org/10.1128/IAI.00476-17. Muraoka, W. T., & Zhang, Q. (2011). Phenotypic and
Macpherson, A. J., & McCoy, K. D. (2015). Standardised genotypic evidence for L-fucose utilization by Cam-
animal models of host microbial mutualism. Mucosal pylobacter jejuni. Journal of Bacteriology, 193,
Immunology, 8, 476–486. 1065–1075.
Madhavan, T. P., & Sakellaris, H. (2015). Colonization Ng, K. M., Ferreyra, J. A., Higginbottom, S. K., Lynch,
factors of enterotoxigenic Escherichia coli. Advances J. B., Kashyap, P. C., Gopinath, S., Naidu, N.,
in Applied Microbiology, 90, 155–197. Choudhury, B., Weimer, B. C., Monack, D. M., et al.
Maier, L., Vyas, R., Cordova, C. D., Lindsay, H., Schmidt, (2013). Microbiota-liberated host sugars facilitate post-
T. S. B., Brugiroux, S., Periaswamy, B., Bauer, R., antibiotic expansion of enteric pathogens. Nature, 502,
Sturm, A., Schreiber, F., et al. (2013). Microbiota-derived 96–99.
hydrogen fuels Salmonella typhimurium invasion of the Nguyen, T. L., Vieira-Silva, S., Liston, A., & Raes,
gut ecosystem. Cell Host and Microbe, 14, 641–651. J. (2015). How informative is the mouse for human
McCoy, K. D., Ronchi, F., & Geuking, M. B. (2017). gut microbiota research? Disease Models and
Host-microbiota interactions and adaptive immunity. Mechanisms, 8, 1–16.
Immunological Reviews, 279, 63–69. Nuttal, G., & Thierfelder, H. (1895). Thierisches Leben
McGovern, D. P., Jones, M. R., Taylor, K. D., Marciante, ohne Bakterien im Verdauungskanal. Hoppe-Seyler’s
K., Yan, X., Dubinsky, M., Ippoliti, A., Vasiliauskas, Zeitschrift für Physiologische Chemie, 21, 109–121.
E., Berel, D., Derkowski, C., et al. (2010). O’Neill, L. A. J., Kishton, R. J., & Rathmell, J. (2016). A
Fucosyltransferase 2 (FUT2) non-secretor status is guide to immunometabolism for immunologists.
associated with Crohn’s disease. Human Molecular Nature Reviews. Immunology, 16, 553–565.
Genetics, 19, 3468–3476. Ohno, H. (2016). Intestinal M cells. Journal of Biochem-
McGuckin, M. A., Lindén, S. K., Sutton, P., & Florin, istry, 159, 151–160.
T. H. (2011). Mucin dynamics and enteric pathogens. Okai, S., Usui, F., Ohta, M., Mori, H., Kurokawa, K.,
Nature Reviews. Microbiology, 9, 265–278. Matsumoto, S., Kato, T., Miyauchi, E., Ohno, H., &
Miller, C. P., Bohnhoff, M., & Drake, B. L. (1954). The Shinkura, R. (2017). Intestinal IgA as a modulator of
effect of antibiotic therapy on susceptibility to an the gut microbiota. Gut Microbes, 8, 486–492.
experimental enteric infection. Transactions of the Okoro, C. K., Kingsley, R. A., Connor, T. R., Harris, S. R.,
Association of American Physicians, 67, 156–161. Parry, C. M., Al-Mashhadani, M. N., Kariuki, S.,
Mills, S., Shanahan, F., Stanton, C., Hill, C., Coffey, A., & Msefula, C. L., Gordon, M. A., de Pinna, E., et al.
Ross, R. P. (2013). Movers and shakers: Influence of (2012). Intracontinental spread of human invasive Sal-
bacteriophages in shaping the mammalian gut monella Typhimurium pathovariants in sub-Saharan
microbiota. Gut Microbes, 4, 4–16. Africa. Nature Genetics, 44, 1215–1221.
Minot, S., Bryson, A., Chehoud, C., Wu, G. D., Lewis, Olsan, E. E., Byndloss, M. X., Faber, F., Rivera-Chávez,
J. D., & Bushman, F. D. (2013). Rapid evolution of the F., Tsolis, R. M., & Bäumler, A. J. (2017). Coloniza-
human gut virome. Proceedings of the National Acad- tion resistance: The deconvolution of a complex trait.
emy of Sciences of the United States of America, 110, The Journal of Biological Chemistry, 292, 8577–8581.
12450–12455. Pabst, O., Cerovic, V., & Hornef, M. (2016). Secretory
Molnár, A., Hess, C., Pál, L., Wágner, L., Awad, W. A., IgA in the coordination of establishment and mainte-
Husvéth, F., Hess, M., & Dublecz, K. (2015). Compo- nance of the microbiota. Trends in Immunology, 37,
sition of diet modifies colonization dynamics of 287–296.
Pacheco, A. R., Curtis, M. M., Ritchie, J. M., Munera, D., Chu, H., Santos, R. L., Berger, T., et al. (2009).
Waldor, M. K., Moreira, C. G., & Sperandio, Lipocalin-2 resistance confers an advantage to Salmo-
V. (2012). Fucose sensing regulates bacterial intestinal nella enterica serotype Typhimurium for growth and
colonization. Nature, 492, 113–117. survival in the inflamed intestine. Cell Host and
Palm, N. W., de Zoete, M. R., & Flavell, R. A. (2015). Microbe, 5, 476–486.
Immune-microbiota interactions in health and disease. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F.,
Clinical Immunology (Orlando, Florida), 159, Edberg, S., & Medzhitov, R. (2004). Recognition of
122–127. commensal microflora by toll-like receptors is required
Perdicchio, M., Ilarregui, J. M., Verstege, M. I., for intestinal homeostasis. Cell, 118, 229–241.
Cornelissen, L. A. M., Schetters, S. T. T., Engels, S., Ramachandran, G., Panda, A., Higginson, E. E., Ateh, E.,
Ambrosini, M., Kalay, H., Veninga, H., den Haan, Lipsky, M. M., Sen, S., Matson, C. A., Permala-Booth,
J. M. M., et al. (2016). Sialic acid-modified antigens J., DeTolla, L. J., & Tennant, S. M. (2017). Virulence
impose tolerance via inhibition of T-cell proliferation of invasive Salmonella Typhimurium ST313 in animal
and de novo induction of regulatory T cells. models of infection. PLoS Neglected Tropical
Proceedings of the National Academy of Sciences of Diseases, 11, e0005697.
the United States of America, 113, 3329–3334. Rausch, P., Steck, N., Suwandi, A., Seidel, J. A., Künzel,
Perez-Lopez, A., Behnsen, J., Nuccio, S.-P., & Raffatellu, S., Bhullar, K., Basic, M., Bleich, A., Johnsen, J. M.,
M. (2016). Mucosal immunity to pathogenic intestinal Vallance, B. A., et al. (2015). Expression of the blood-
bacteria. Nature Reviews. Immunology, 16, 135–148. group-related gene B4galnt2 alters susceptibility to
Phongsisay, V. (2016). The immunobiology of Campylo- Salmonella infection. PLoS Pathogens, 11, e1005008.
bacter jejuni: Innate immunity and autoimmune Ringot-Destrez, B., Kalach, N., Mihalache, A., Gosset, P.,
diseases. Immunobiology, 221, 535–543. Michalski, J.-C., Léonard, R., & Robbe-Masselot,
Phongsisay, V., Hara, H., & Fujimoto, S. (2015). Toll-like C. (2017). How do they stick together? Bacterial
receptors recognize distinct proteinase-resistant adhesins implicated in the binding of bacteria to the
glycoconjugates in Campylobacter jejuni and human gastrointestinal mucins. Biochemical Society
Escherichia coli. Molecular Immunology, 64, 195–203. Transactions, 45, 389–399.
Pickard, J. M., Maurice, C. F., Kinnebrew, M. A., Abt, Robinson, C. M., & Pfeiffer, J. K. (2014). Viruses and the
M. C., Schenten, D., Golovkina, T. V., Bogatyrev, microbiota. Annual Review of Virology, 1, 55–69.
S. R., Ismagilov, R. F., Pamer, E. G., Turnbaugh, Ruiz-Palacios, G. M., Cervantes, L. E., Ramos, P.,
P. J., et al. (2014). Rapid fucosylation of intestinal Chavez-Munguia, B., & Newburg, D. S. (2003). Cam-
epithelium sustains host-commensal symbiosis in sick- pylobacter jejuni binds intestinal H(O) antigen (Fuc
ness. Nature, 514, 638–641. alpha 1, 2Gal beta 1, 4GlcNAc), and fucosyloligosac-
Planer, J. D., Peng, Y., Kau, A. L., Blanton, L. V., Ndao, charides of human milk inhibit its binding and infec-
I. M., Tarr, P. I., Warner, B. B., & Gordon, J. I. (2016). tion. The Journal of Biological Chemistry, 278,
Development of the gut microbiota and mucosal IgA 14112–14120.
responses in twins and gnotobiotic mice. Nature, 534, Sana, T. G., Flaugnatti, N., Lugo, K. A., Lam, L. H.,
263–266. Jacobson, A., Baylot, V., Durand, E., Journet, L.,
Price-Carter, M., Tingey, J., Bobik, T. A., & Roth, J. R. Cascales, E., & Monack, D. M. (2016). Salmonella
(2001). The alternative electron acceptor tetrathionate Typhimurium utilizes a T6SS-mediated antibacterial
supports B12-dependent anaerobic growth of Salmo- weapon to establish in the host gut. Proceedings of
nella enterica serovar typhimurium on ethanolamine or the National Academy of Sciences of the United States
1,2-propanediol. Journal of Bacteriology, 183, of America, 113, E5044–E5051.
2463–2475. Sankar, S. A., Lagier, J.-C., Pontarotti, P., Raoult, D., &
Próchnicki, T., & Latz, E. (2017). Inflammasomes on the Fournier, P.-E. (2015). The human gut microbiome, a
crossroads of innate immune recognition and meta- taxonomic conundrum. Systematic and Applied Micro-
bolic control. Cell Metabolism, 26, 71–93. biology, 38, 276–286.
Pukatzki, S., Ma, A. T., Revel, A. T., Sturtevant, D., & Sassone-Corsi, M., & Raffatellu, M. (2013). A hydrogen
Mekalanos, J. J. (2007). Type VI secretion system boost for salmonella. Cell Host and Microbe, 14,
translocates a phage tail spike-like protein into target 603–604.
cells where it cross-links actin. Proceedings of the Sassone-Corsi, M., Nuccio, S.-P., Liu, H., Hernandez, D.,
National Academy of Sciences of the United States of Vu, C. T., Takahashi, A. A., Edwards, R. A., &
America, 104, 15508–15513. Raffatellu, M. (2016). Microcins mediate competition
Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., among Enterobacteriaceae in the inflamed gut. Nature,
Manichanh, C., Nielsen, T., Pons, N., Levenez, F., 540, 280–283.
Yamada, T., et al. (2010). A human gut microbial Sears, C. L. (2009). Enterotoxigenic Bacteroides fragilis:
gene catalogue established by metagenomic sequenc- A rogue among symbiotes. Clinical Microbiology
ing. Nature, 464, 59–65. Reviews, 22, 349–369 Table of Contents.
Raffatellu, M., George, M. D., Akiyama, Y., Hornsby, Sperandio, B., Fischer, N., & Sansonetti, P. J. (2015).
M. J., Nuccio, S.-P., Paixao, T. A., Butler, B. P., Mucosal physical and chemical innate barriers:
Lessons from microbial evasion strategies. Seminars in Szymanski, C. M., & Gaynor, E. C. (2012). How a sugary
Immunology, 27, 111–118. bug gets through the day: Recent developments in
Spiga, L., Winter, M. G., Furtado de Carvalho, T., Zhu, understanding fundamental processes impacting Cam-
W., Hughes, E. R., Gillis, C. C., Behrendt, C. L., Kim, pylobacter jejuni pathogenesis. Gut Microbes, 3,
J., Chessa, D., Andrews-Polymenis, H. L., et al. 135–144.
(2017). An oxidative central metabolism enables Sal- Tailford, L. E., Crost, E. H., Kavanaugh, D., & Juge,
monella to utilize microbiota-derived succinate. Cell N. (2015). Mucin glycan foraging in the human gut
Host and Microbe, 22, 291–301.e6. microbiome. Frontiers in Genetics, 6, 81.
St Charles, J. L., Bell, J. A., Gadsden, B. J., Malik, A., Tan, T. G., Sefik, E., Geva-Zatorsky, N., Kua, L., Naskar,
Cooke, H., Van de Grift, L. K., Kim, H. Y., Smith, D., Teng, F., Pasman, L., Ortiz-Lopez, A., Jupp, R.,
E. J., & Mansfield, L. S. (2017). Guillain Barré syn- Wu, H.-J. J., et al. (2016). Identifying species of sym-
drome is induced in non-obese diabetic (NOD) mice biont bacteria from the human gut that, alone, can
following Campylobacter jejuni infection and is induce intestinal Th17 cells in mice. Proceedings of
exacerbated by antibiotics. Journal of Autoimmunity, the National Academy of Sciences of the United States
77, 11–38. of America, 113, E8141–E8150.
Stahl, M., Friis, L. M., Nothaft, H., Liu, X., Li, J., Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016).
Szymanski, C. M., & Stintzi, A. (2011). L-fucose The microbiome and innate immunity. Nature, 535,
utilization provides Campylobacter jejuni with a com- 65–74.
petitive advantage. Proceedings of the National Acad- Thiennimitr, P., Winter, S. E., Winter, M. G., Xavier,
emy of Sciences of the United States of America, 108, M. N., Tolstikov, V., Huseby, D. L., Sterzenbach, T.,
7194–7199. Tsolis, R. M., Roth, J. R., & Bäumler, A. J. (2011).
Staubach, F., Künzel, S., Baines, A. C., Yee, A., McGee, Intestinal inflammation allows Salmonella to use etha-
B. M., Bäckhed, F., Baines, J. F., & Johnsen, J. M. nolamine to compete with the microbiota. Proceedings
(2012). Expression of the blood-group-related of the National Academy of Sciences of the United
glycosyltransferase B4galnt2 influences the intestinal States of America, 108, 17480–17485.
microbiota in mice. The ISME Journal, 6, 1345–1355. Thursby, E., & Juge, N. (2017). Introduction to the human
Stecher, B., & Hardt, W. D. (2011). Mechanisms gut microbiota. Biochemical Journal, 474, 1823–1836.
controlling pathogen colonization of the gut. Current Turonova, H., Neu, T. R., Ulbrich, P., Pazlarova, J., &
Opinion in Microbiology, 14, 82–91. Tresse, O. (2016). The biofilm matrix of Campylobac-
Stecher, B., Barthel, M., Schlumberger, M. C., Haberli, L., ter jejuni determined by fluorescence lectin-binding
Rabsch, W., Kremer, M., & Hardt, W. D. (2008). analysis. Biofouling, 32, 597–608.
Motility allows S. Typhimurium to benefit from the Ursell, L. K., Metcalf, J. L., Parfrey, L. W., & Knight,
mucosal defence. Cellular Microbiology, 10, R. (2012). Defining the human microbiome. Nutrition
1166–1180. Reviews, 70(Suppl 1), S38–S44.
Stecher, B., Berry, D., & Loy, A. (2013). Colonization van der Heijden, J., & Finlay, B. B. (2012). Type III
resistance and microbial ecophysiology: Using gnoto- effector-mediated processes in Salmonella infection.
biotic mouse models and single-cell technology to Future Microbiology, 7, 685–703.
explore the intestinal jungle. FEMS Microbiology van Sorge, N. M., Bleumink, N. M. C., van Vliet, S. J.,
Reviews, 37, 793–829. Saeland, E., van der Pol, W.-L., van Kooyk, Y., & van
Stephenson, H. N., John, C. M., Naz, N., Gundogdu, O., Putten, J. P. M. (2009). N-glycosylated proteins and
Dorrell, N., Wren, B. W., Jarvis, G. A., & Bajaj-Elliott, distinct lipooligosaccharide glycoforms of Campylo-
M. (2013). Campylobacter jejuni lipooligosaccharide bacter jejuni target the human C-type lectin receptor
sialylation, phosphorylation, and amide/ester linkage MGL. Cellular Microbiology, 11, 1768–1781.
modifications fine-tune human Toll-like receptor 4 acti- Verster, A. J., Ross, B. D., Radey, M. C., Bao, Y., Good-
vation. The Journal of Biological Chemistry, 288, man, A. L., Mougous, J. D., & Borenstein, E. (2017).
19661–19672. The landscape of type VI secretion across human gut
Stephenson, H. N., Mills, D. C., Jones, H., Milioris, E., microbiomes reveals its role in community composi-
Copland, A., Dorrell, N., Wren, B. W., Crocker, P. R., tion. Cell Host and Microbe, 22, 411–419.e4.
Escors, D., & Bajaj-Elliott, M. (2014). Pseudaminic Vogt, S. L., Peña-Díaz, J., & Finlay, B. B. (2015). Chemi-
acid on Campylobacter jejuni flagella modulates den- cal communication in the gut: Effects of microbiota-
dritic cell IL-10 expression via Siglec-10 receptor: A generated metabolites on gastrointestinal bacterial
novel flagellin-host interaction. The Journal of Infec- pathogens. Anaerobe, 34, 106–115.
tious Diseases, 210, 1487–1498. Vorwerk, H., Mohr, J., Huber, C., Wensel, O., Schmidt-
Struwe, W. B., Gough, R., Gallagher, M. E., Kenny, D. T., Hohagen, K., Gripp, E., Josenhans, C., Schomburg, D.,
Carrington, S. D., Karlsson, N. G., & Rudd, P. M. Eisenreich, W., & Hofreuter, D. (2014). Utilization of
(2015). Identification of O-glycan structures from host-derived cysteine-containing peptides overcomes
chicken intestinal mucins provides insight into the restricted sulphur metabolism of Campylobacter
Campylobactor jejuni pathogenicity. Molecular and jejuni. Molecular Microbiology, 93, 1224–1245.
Cellular Proteomics, 14, 1464–1477.
Vorwerk, H., Huber, C., Mohr, J., Bunk, B., Bhuju, S., Yin, Y., Fan, B., Liu, W., Ren, R., Chen, H., Bai, S., Zhu,
Wensel, O., Spröer, C., Fruth, A., Flieger, A., Schmidt- L., Sun, G., Yang, Y., & Wang, X. (2017). Investiga-
Hohagen, K., et al. (2015). A transferable plasticity tion into the stability and culturability of Chinese
region in Campylobacter coli allows isolates of an enterotypes. Scientific Reports, 7, 7947.
otherwise non-glycolytic food-borne pathogen to Young, N. M., Brisson, J. R., Kelly, J., Watson, D. C.,
catabolize glucose. Molecular Microbiology, 98, Tessier, L., Lanthier, P. H., Jarrell, H. C., Cadotte, N.,
809–830. St Michael, F., Aberg, E., et al. (2002). Structure of the
Wagley, S., Newcombe, J., Laing, E., Yusuf, E., Sambles, N-linked glycan present on multiple glycoproteins in
C. M., Studholme, D. J., La Ragione, R. M., Titball, the Gram-negative bacterium, Campylobacter jejuni.
R. W., & Champion, O. L. (2014). Differences in The Journal of Biological Chemistry, 277,
carbon source utilisation distinguish Campylobacter 42530–42539.
jejuni from Campylobacter coli. BMC Microbiology, Young, K. T., Davis, L. M., & Dirita, V. J. (2007). Cam-
14, 262. pylobacter jejuni: Molecular biology and pathogenesis.
Wagner, C., Barlag, B., Gerlach, R. G., Deiwick, J., & Nature Reviews. Microbiology, 5, 665–679.
Hensel, M. (2014). The Salmonella enterica giant Yrios, J. W., & Balish, E. (1986). Pathogenesis of Cam-
adhesin SiiE binds to polarized epithelial cells in a pylobacter spp. in athymic and euthymic germfree
lectin-like manner. Cellular Microbiology, 16, 962–975. mice. Infection and Immunity, 53, 384–392.
Winter, S. E., & Bäumler, A. J. (2011). A breathtaking Yurist-Doutsch, S., Arrieta, M.-C., Vogt, S. L., & Finlay,
feat: To compete with the gut microbiota, Salmonella B. B. (2014). Gastrointestinal microbiota-mediated
drives its host to provide a respiratory electron accep- control of enteric pathogens. Annual Review of Genet-
tor. Gut Microbes, 2, 58–60. ics, 48, 361–382.
Winter, S. E., Thiennimitr, P., Winter, M. G., Butler, B. P., Zasloff, M. (2002). Antimicrobial peptides in health and
Huseby, D. L., Crawford, R. W., Russell, J. M., disease. The New England Journal of Medicine, 347,
Bevins, C. L., Adams, L. G., Tsolis, R. M., et al. 1199–1200.
(2010). Gut inflammation provides a respiratory elec- Zhu, W., Winter, M. G., Byndloss, M. X., Spiga, L.,
tron acceptor for Salmonella. Nature, 467, 426–429. Duerkop, B. A., Hughes, E. R., Büttner, L., de Lima
Wu, S., Rhee, K.-J., Albesiano, E., Rabizadeh, S., Wu, X., Romão, E., Behrendt, C. L., Lopez, C. A., et al. (2018).
Yen, H.-R., Huso, D. L., Brancati, F. L., Wick, E., Precision editing of the gut microbiota ameliorates
McAllister, F., et al. (2009). A human colonic com- colitis. Nature, 553, 208–211.
mensal promotes colon tumorigenesis via activation of Zumbrun, S. D., Melton-Celsa, A. R., Smith, M. A.,
T helper type 17 T cell responses. Nature Medicine, 15, Gilbreath, J. J., Merrell, D. S., & O’Brien, A. D.
1016–1022. (2013). Dietary choice affects Shiga toxin-producing
Yatsunenko, T., Rey, F. E., Manary, M. J., Trehan, I., Escherichia coli (STEC) O157:H7 colonization and
Dominguez-Bello, M. G., Contreras, M., Magris, M., disease. Proceedings of the National Academy of
Hidalgo, G., Baldassano, R. N., Anokhin, A. P., et al. Sciences of the United States of America, 110,
(2012). Human gut microbiome viewed across age and E2126–E2133.
geography. Nature, 486, 222–227.

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Microbiome and Diseases: Pathogen

Abstract how intestinal pathogenic agents can interact

# Springer International Publishing AG, part of Springer Nature 2018 209

Immune evasion, Adherence and secretion of toxins Mucus invasion, Motility

nitrate tetrathionate SPI-1

(CD toxin) B. fragilis (ETBF; BFT fragilysin)

cell death necrosis, lesions, loss of barrier function

Salmonella Campylobacter (jejuni, coli)

protease resistance, mucus-invasive motility

fucose sialic acid 1,2 propanediol microbiota-derived glycan

activated by commensal bacteria or their products

3. Can we deﬁne a universal core consortium

1. Original description of intestinal

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