REVIEW

published: 17 April 2019

doi: 10.3389/fnut.2019.00047

The Effects of Vegetarian and Vegan

Diets on Gut Microbiota
Aleksandra Tomova 1*, Igor Bukovsky 2 , Emilie Rembert 3 , Willy Yonas 3 , Jihad Alwarith 3 ,
Neal D. Barnard 3,4 and Hana Kahleova 3
1
Faculty of Medicine, Institute of Physiology, Comenius University in Bratislava, Bratislava, Slovakia, 2 Center for Clinical
Nutrition, Bratislava, Slovakia, 3 Physicians Committee for Responsible Medicine, Washington, DC, United States, 4 Adjunct
Faculty, George Washington University School of Medicine and Health Sciences, Washington, DC, United States

The difference in gut microbiota composition between individuals following vegan or

vegetarian diets and those following omnivorous diets is well documented. A plant-based
diet appears to be beneficial for human health by promoting the development of
more diverse and stable microbial systems. Additionally, vegans and vegetarians have
significantly higher counts of certain Bacteroidetes-related operational taxonomic units
compared to omnivores. Fibers (that is, non-digestible carbohydrates, found exclusively
in plants) most consistently increase lactic acid bacteria, such as Ruminococcus, E.
rectale, and Roseburia, and reduce Clostridium and Enterococcus species. Polyphenols,
also abundant in plant foods, increase Bifidobacterium and Lactobacillus, which provide
anti-pathogenic and anti-inflammatory effects and cardiovascular protection. High fiber
intake also encourages the growth of species that ferment fiber into metabolites
Edited by: as short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. The
Sergueï O. Fetissov,
Université de Rouen, France positive health effects of SCFAs are myriad, including improved immunity against
Reviewed by: pathogens, blood–brain barrier integrity, provision of energy substrates, and regulation
Iolanda Cioffi, of critical functions of the intestine. In conclusion, the available literature suggests that a
Azienda Ospedaliera Universitaria
Federico II, Italy
vegetarian/vegan diet is effective in promoting a diverse ecosystem of beneficial bacteria
Christine Ann Butts, to support both human gut microbiome and overall health. This review will focus on
The New Zealand Institute for Plant & effects of different diets and nutrient contents, particularly plant-based diets, on the gut
Food Research Ltd, New Zealand
microbiota composition and production of microbial metabolites affecting the host health.
*Correspondence:
Aleksandra Tomova Keywords: gut microbiota, fiber, nutrition, plant-based diet, postbiotics
[email protected]

Specialty section: INTRODUCTION

This article was submitted to
Clinical Nutrition, Recent studies of the human microbiome have emerged as an area of popular interest. For decades,
a section of the journal
many investigations have elucidated the impact of the human gut microbiota on the physiology of
Frontiers in Nutrition
the host, with new and unexpectedly broad implications for health and disease.
Received: 11 January 2019 The human microbiota, defined as the total of all microbial taxa associated with human
Accepted: 29 March 2019
beings (bacteria, viruses, fungi, protozoa, archaea), consists of a newly estimated 3 × 1013
Published: 17 April 2019
(trillion) microbes harbored by each person (1). The term microbiome is often incorrectly used
Citation: interchangeably with the term microbiota. However, microbiome refers to the catalog of these
Tomova A, Bukovsky I, Rembert E,
microbes and their genes. The human gut microbiome represents ∼3.3 million non-redundant
Yonas W, Alwarith J, Barnard ND and
Kahleova H (2019) The Effects of
microbial genes, which outnumbers the human genome of some 21,000 genes in the ratio of
Vegetarian and Vegan Diets on Gut ∼150:1 (2). Interestingly, the diversity among the microbiomes of two different individuals is vast
Microbiota. Front. Nutr. 6:47. compared to their human genomic variation; humans are about 99.9% identical to each other in
doi: 10.3389/fnut.2019.00047 terms of their genome (3), but their gut microbiome can be up to 80–90% different (4).

Frontiers in Nutrition | www.frontiersin.org 1 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

Recent advancements in laboratory techniques have revealed and effects on the enteric nervous system, local immunity, brain,
functions of the human gut microbiota related to immunity and and genes.
the gastrointestinal, brain, and cardiovascular systems. Research
has also suggested a profound effect of the human gut microbiota
on host cells and genes. This extensive interaction has suggested
EFFECT OF DIET ON GUT MICROBIOTA
that the microbiome functions effectively as a separate “organ.” COMPOSITION
Several studies have suggested that there are three basic
bacterial enterotypes (5) (1) genus Prevotella (considered to be The difference in gut microbiota composition between
mostly anti-inflammatory and otherwise protective), (2) genus individuals consuming a vegan/vegetarian and an omnivorous
Bacteroides (more pro-inflammatory and possibly related to the diet is well documented. Research shows that vegetarian/vegan
heightened risk of metabolic syndrome and other pathological diets foster different microbiota when compared to omnivores,
conditions), and (3) genus Ruminococcus (of which the biological with only a marginal difference between vegans and vegetarians
significance is less evident) (6). (23). Changes in microbiota composition might be due to
An imbalance of the gut microbiota has been linked differences in bacteria directly consumed through food,
with gastrointestinal conditions such as reflux, peptic ulcers, differences in substrates consumed, variations in transit
irritable bowel syndrome, non-alcoholic steatohepatitis, and time through the gastrointestinal system, pH, host secretion
inflammatory bowel disease. Additionally, some systemic influenced by dietary patterns, and regulation of gene expression
conditions such as obesity, atherosclerosis, type 2 diabetes, of the host himself and/or his/her microbiota (24).
cancer, Alzheimer’s and Parkinson’s disease, amyotrophic lateral A plant-based diet appears to be beneficial for human health
sclerosis, autism spectrum disorder, atopy etc., also appear to be by promoting the development of a more diverse gut microbial
linked to unfavorable changes in gut microbiota composition system, or even distribution of different species (25, 26).
(7–17). An accumulating body of evidence points to the gut
microbiota as a mediator of dietary impact on the host metabolic Diversity and Richness of the Gut
status. Current research is focusing on the establishment Microbiota
of causal relationships in people and the development of The diversity of the microbiota appears to have an important
therapeutic interventions such as personalized nutrition (18). association with BMI, obesity, and arterial compliance; and
Dietary composition appears to have long-term and acute a majority of the research suggests that a plant-based diet
effects on the gut microbiota ecosystem (19, 20). Different long- fosters a greater microbial diversity. Klimenko et al. found a
term dietary patterns, such as vegetarian/vegan vs. omnivorous positive association between alpha-diversity, or local microbial
diets, have significant influence on gut microbiota composition. richness, and long-term fruit and vegetable intake (p < 0.05)
The different gut microbiota content is shown to provide (27). Likewise, Martinez et al. observed that adding whole-grain
different food nutrients metabolites, termed postbiotics. For barley, brown rice, or a mixture of the first two to the diet of
instance, SCFAs, phytoestrogens, or isothiocyanates are more volunteers resulted in an increase in microbial diversity (n = 28)
linked with the plant-based food, while TMAO and secondary (28). Klimenko et al. also found a negative association between
bile acids with the meat-based diet. These and other postbiotics alpha-diversity and BMI (p < 0.05) (27).
take part in the metabolism of the host in different ways. This However, a short-term dietary intervention advising increased
review will focus on some general as well as specific aspects of fiber consumption resulted in a slight but significant decrease in
this dynamic field of research. diversity (p < 0.001). The researchers suggest this reduction in
diversity might be the result of a rapid dietary change resulting
in a temporary disruption to the microbial composition. This
GUT MICROBIOTA: GENERAL ASPECTS hypothesis of transitory microbial “stress” also explains the
slight but significant increase in Enterobacteriaceae as a result
In addition to bacteria, the gut is host to multiple kingdoms: of the intervention (p < 0.05). Enterobacteriaceae abundance is
archaea, viruses, and eukaryotes, including fungal species. The typically lower on a vegan diet vs. an omnivorous one (P <
gut microbiota is represented by more than 1,000 microbial 0.05) (29). This is likely due to the greater presence of butyrate-
species, belonging primary to just two phyla: Bacteroidetes and producing bacteria on a higher fiber diet, which can lower
Firmicutes (21). Based on human stool samples, overall, the colonic pH, preventing the growth of pathogenic bacteria, such
genera Bacteroides, Prevotella, Bifidobacterium, Eubacterium, as Enterobacteriaceae (30).
Clostridium, Streptococcus, and Enterobacteriaceae are most Verdam et al. observed reduced microbial diversity in obese
commonly found. It should be noted that stool samples provide vs. non-obese study participants (n = 28). The obese participants
reasonable estimations of the gut microbiota rather than a also displayed a reduction in the Bacteriodetes:Firmicutes
complete representation (22). This is because anaerobic species ratio and an increase in Proteobacteria, a pro-inflammatory
often attach to the gut mucosa, making it difficult to identify all phylum. Likewise, an increase in C-reactive protein was
bacterial species present in the large intestine. Also, it is probable observed (p < 0.001) which inversely correlated with the
that the biological significance of any genera or species is not Bacteriodetes:Firmicutes ratio (p < 0.05). These observations
given by its relative proportion in the whole ecosystem. Rather, suggest a pro-inflammatory effect of obesity-related microbiota
its significance is observed through its metabolism/postbiotics (31). On the other hand, participants from the Adventist Health

Frontiers in Nutrition | www.frontiersin.org 2 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

Study-2 (60,903) following a vegan diet displayed the lowest abundance of Firmicutes was twice as much in the Italian children
BMI values when compared with those following a vegetarian than in the Burkina Faso children (63.7 vs. 27.3%, respectively).
or omnivorous diet (32). These findings indicate that a vegan The abundance of Bacteroidetes in the Italian children was
diet, associated with lower body weight, might benefit microbial less than half of that seen than in the Burkina Faso children
diversity and protect against inflammation. (22.4 vs. 57.7%, respectively). A decrease in Firmicutes levels,
Menni et al. observed that carotid-femoral pulse wave usually occurring in favor of Bacteroidetes and Bifidobacteria,
velocity, a measure of arterial stiffness, was negatively associated as seen in response to an increase in resistant starches, may
with microbiome diversity (p = 0.001) in women (n = 617) be beneficial in preventing and treating obesity (41). While
(33). This correlation remained significant after adjusting for these correlations between diet and microbiota composition
insulin resistance and visceral fat. Arterial stiffness is oftentimes are observed among different populations, it is important to
caused by hyperglycemia or hyperinsulinemia (34) and is consider other factors that may play a role, such as ethnicity, host
significantly correlated with inflammatory adipokine levels. The genotypes, environmental factors, etc.
researchers suggest the association between arterial stiffness and Research has shown that the balance of Bacteroidetes and
microbial diversity can be explained partially by the role of the Firmicutes is an important marker for obesity and higher
gut in modulating systemic inflammation. Thus, an increase BMI. Specifically, a decreased Bacteroidetes:Firmicutes ratio has
in microbial diversity might improve systemic inflammation, a strong negative correlation with BMI (rs = 0.59, P <
thereby reducing arterial stiffness. 0.001) (31). A possible explanation for this correlation may
Additionally, vegans and vegetarians have a significantly be found in the observation that a 20% increase in Firmicutes
greater richness (alpha diversity) compared to omnivores, and a corresponding decrease in Bacteroidetes abundance is
specifically counts of certain Bacteroidetes-related operational associated with a 150 kcal/day increase in energy harvest,
taxonomic units (OTUs) (35). It seems likely that many health resulting in weight gain overtime. Therefore, an increased
benefits of vegetarian/vegan diets are, in part, mediated by Bacteroidetes:Firmicutes ratio, as seen on a high fiber, plant-
the gut microbiota—not only through the higher relative based diet, may result in weight loss by reducing the amount
abundance of those OTUs that are currently considered to be of energy extracted from the diet. Further research is needed
protective (Bacteroidetes, Prevotella, Roseburia, etc.), but also to determine whether the increase in energy harvest due is
from postbiotic and epigenetic effects on various risk factors for due to the Bacteroidetes:Firmicutes ratio promoting adiposity or
chronic inflammation and chronic degenerative diseases (36). representing a host-mediated adaptive response to limit energy
uptake (42).
Studies have also shown opposite trends in Firmicutes and
Effects of Diet on the Bacteroidetes. One study compared US children eating a Western
Bacteroidetes:Firmicutes Ratio diet to Bangladeshi children consuming a plant-based diet of
Despite significant inter-individual differences, a healthy adult rice, bread, and lentils. The Bacteroidetes:Firmicutes ratio was
intestinal microbiome is characterized by the dominance of these three times higher in the US children consuming the Western
Bacteroidetes-related OTUs along with those of the Firmicutes diet (43). This opposes the previous prediction of a Western
phylum (37, 38). Research has shown variability in these phyla diet resulting in a decreased Bacteroidetes:Firmicutes ratio. The
concentrations to be heavily affected by diet, specifically the researchers noted age and geographical differences as potential
ratio between the two when comparing omnivorous diets of explanation for this departure from the expected ratio, as well
the type common in North America, vs. a vegetarian/vegan as inter-subject variability. Another study asked participants
diet. One study compared the bacterial composition between to increase their fiber consumption and avoid Western diet
Indian (n = 11) and Chinese (n = 5) adults (39). While foods. While prior studies would have suggested an increase
both populations ate diets centered around carbohydrates and in Bacteroidetes:Firmicutes, the ratio decreased (0.13 ± 0.2 to
vegetables, the Chinese diet was heavier in animal fat and protein 0.03 ± 0.09, Wilcoxon paired test p < 0.0001, n = 430) (27).
than the Indian diet of whole grains and plant-based vegetarian Another study analyzed the microbial composition of lean and
foods. The percentage of Bacteroidetes within the microbiomes obese subjects (n = 98) and observed that, when compared to
of Indian participants was nearly four times greater than in the lean subjects, overweight and obese volunteers presented a higher
Chinese, 16.39% vs. 4.27%, respectively (p = 0.001). The higher ratio Bacteroidetes to Firmicutes (P = 0.001 and P = 0.005,
abundance of Bacteroidetes in Indians was hypothesized to be respectively) (44). Likewise, comparison of bacterial phyla did
due to their lower consumption of animal products; indicating not show a significant difference in the Bacteroidetes to Firmicutes
a diet lower in animal products to be associated with greater ratio between obese and lean volunteers (n = 20) (45). These
Bacteroidetes counts. examples reflect the difficulties in broadly linking certain phyla
Another study compared the fecal microbiota of Italian to particular diets. The primary challenge in analyzing specific
children (n = 15) vs. the fecal microbiota of children living in a microbiota is the need to consider the state and interaction
rural western Africa, specifically in Burkina Faso (n = 14) (40). dynamic of microbes encompassing the whole microbiome.
The Italian children typically consumed a Western diet, high
in animal protein, sugar, starch, and fat and low in fiber. The Effects of Diet on Enterotypes
African children of Burkina Faso consumed a diet low in fat and As mentioned above, there are three main enterotypes
animal protein and rich in starch, fiber, and plant protein. The observed in human microbiomes: Prevotella, Bacteroides,

Frontiers in Nutrition | www.frontiersin.org 3 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

and Ruminococcus. Prevotella, a genus of the Bacteroidetes microbes degrade complex carbohydrates, they also break down
phyla, appears to be significantly richer in response to a vegan the resistant starches found in refined grain products (52).
diet. In the previously mentioned study by De Filippo et al., Ruminococcus might also play a role in the conversion of
Prevotella was exclusively present in the children of Burkina animal-derived choline to trimethylamine (TMA) (53). Thus, the
Faso consuming a diet low in fat and animal protein and rich in abundance of Ruminococcus is influenced by both animal and
starch, fiber, and plant protein when compared to children living plant based diets.
in Italy consuming a Western diet, high in animal protein, sugar,
starch, and fat, and low in fiber (40). Another study compared Effects of Diet on Additional Bacteria
the diets of 178 elderly residents living in either the community While Bacteroides can be pro-inflammatory and their
or in long-term residential care (46). The community group was concentration is associated with long term consumption
found to consume a low to medium fat, high fiber diet; while the of animal products, a study analyzing 11 vegetarians, 20
residents in long-term care consumed a moderate to high in fat, vegans, and 29 omnivores (49) found a discrepancy in this
and low fiber diet. The study found that those in the community, generalization. In addition to finding Clostridium clostridioforme
eating a profile more reflective of a plant-based diet, more and Faecalibacterium prausnitzii, both considered to be health
frequently had gut communities of the Prevotella enterotype. protective, in higher relative abundance in the vegetarians/vegans
The study comparing Indian and Chinese adults shows similar compared to the omnivores, Bacteroides thetaiotaomicron was
results (39). As expected, the Indians who were consuming less also observed in higher abundance in these groups. This
animal products and more plant-based foods than the Chinese discrepancy in categorizing bacteria abundance under a plant-
had a significantly greater percentage of Prevotella (13.07 vs. based diet vs. animal-based diet is not uncommon. Clostridium
0.58%, respectively). When the abundance of Prevotella was cluster XIVa was found in lower ratio in the vegetarian/vegans,
analyzed in Thai vegetarians vs. non-vegetarians, the vegetarians contrary to a study showing Clostridium cluster XIVa bacteria to
were found to have significantly higher numbers of Prevotella (p be a major component of gut microbiota in vegetarian women
= 0.005) (47). Other studies have shown vegan/vegetarian diets, (103). Therefore, while generalizations can be made, some genus
high in plant-based foods, to be associated with high abundances subtypes will be outliers. This discrepancy in some bacterial
of Prevotella (48, 49). This suggests additional support for greater phyla in response to diet has been acknowledged by previous
Prevotella presence in those whom consume less animal products review papers and has been attributed to various reasons, such
and more plant-based food. While mice studies suggest Prevotella as different microbiome profiling methodologies, different
to improve glucose metabolism by improving glycogen storage host genetics, body mass index, and red wine and aspartame
(50), the current lack of any additional research makes Prevotella consumption (54, 55). These are all factors that have been shown
merely a genus to describe an overall ecosystem of human gut to possibly modify our microbiota. Therefore, further studies are
bacteria, primarily under a plant-based diet. warranted in order to isolate their effects from those due to a
Bacteroides, another main enterotype and genus of the plant based vs. omnivorous diet.
Bacteroidetes phyla, also appears to be affected by diet but in Taken together, dietary habits influence the composition of
a different way to Prevotella. Bacteroides has been positively the intestinal microbiota. While dietary changes have a relatively
correlated with long-term diets rich in animal protein and fast impact (51) (within a week) on the microbial composition
saturated fat (20, 27). This is likely due to their ability to and consequently on its metabolites, these effects are modest and
tolerate bile, which is common in gut environments of those reversible (24). For example, changes of microbiota and immune
who consume animal products. In the study mentioned earlier parameters after a 3-month vegetarian diet are significant, but
comparing children in the US eating a Western diet vs. children do not reflect the degree of change that occur with a long-term
in Bangladesh consuming a plant based diet, Bacteroides was the vegetarian diet (56).
major genus in the US children’s microbiota. High proportions of
Bacteroides are found in the gut of humans consuming a Western HOW PLANT FOOD COMPONENTS
diet and the opposite is found in those consuming a high fiber INFLUENCE GUT MICROBIOTA.
diet of fruits and legumes (27, 37, 43, 47, 48).
Ruminococcus is the third major enterotype and is associated Nutrient Bioavailability
with long term fruit and vegetable consumption. Species of this Consuming food nutrients with low bioavailability has recently
genus are specialized in degrading complex carbohydrates, such been found to be important. Lower nutrient bioavailability, found
as cellulose and resistant starch, found in plant based foods in larger food particles, intact plant cell walls, and food without
(51). These microbes degrade dietary fibers, producing butyrate, thermal treatment, means that more nutrients reach lower in the
which acts as an anti-inflammatory compound. Ruminococcus is gastrointestinal system, thus enriching nutrient delivery to the
positively associated with low BMI and negatively associated with gut microbiota (57). This helps support normal gut microbiota
poor lipid profile (27). Likewise, abundance of Rumminococcus development and function (57). Modern westernized diets
has been linked to lower endotoxemia and lower arterial stiffness, contain more ultra-processed foods and acellular nutrients, or
a predictor of cardiovascular risk (33). Walnut consumption has nutrients not containing cells. These components are more easily
been significantly associated with enrichment of Ruminococcus absorbed in the small intestine, depriving the colon of important
as well (38). However, Ruminococcus has also been linked to nutrients, which may alter the composition and metabolism of
low dietary fiber consumption in college students. While these the gut microbiota (58). Acellular food, e.g., sugar, has been

Frontiers in Nutrition | www.frontiersin.org 4 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

shown to induce inflammation in young infants, adolescents, 0.006). Researchers comparing Bifidobacteria levels in vegans,
women of child-bearing age, and older adults. Whole plant foods vegetarians, and controls, found Bifidobacteria to be significantly
have protective effects, favoring the growth of beneficial fiber- lower (p = 0.002) in vegan samples than in controls eating a
degrading bacteria in the colon (58). standard omnivorous diet. No difference between vegans and
vegetarians was observed (29). Another study observed higher
Carbohydrates Bifidobacteria levels in meat eaters compared to participants who
Unlike digestible carbohydrates, non-digestible carbohydrates, switched to a vegetarian diet for 4 weeks after eating a mixed
such as resistance starch, and some sugars, reach the large Western diet, high in fat and meat (58). The relative decrease
intestine where they can be fermented by the gut microbiota of Bifidobacterium in vegetarians and vegans may be explained
to provide energy or produce postbiotics. However, both by a relative abundance of other protective bacteria species,
digestible and non-digestible carbohydrates may influence the such as Prevotella. Prevotella has been observed confers anti-
gut microbiota. Digestible carbohydrates from fruits (e.g., inflammatory effects (40) and can decrease the growth of other
glucose, sucrose, and fructose) have been shown to reduce bacteria by competing for fiber as an energy substrate (61).
Bacteroides and Clostridia (54). Non-digestible carbohydrates A recent in vitro study elucidated the specific mechanism of
most consistently increase lactic acid bacteria, Ruminococcus, E. action of carbohydrates, specifically selected dietary fibers, on gut
rectale, and Roseburia, and reduce Clostridium and Enterococcus microbiota. The study found the following fibers to have differing
species (54). Both digestible and non-digestible carbohydrates prebiotic effects: inulin, alpha-linked galacto-oligosaccharides,
have been shown to increase Bifidobacteria, genus of the beta-linked galacto-oligosaccharides, xylo-oligosaccharides from
Actinobacteria phylum. corn cobs and high-fiber sugar cane, and beta-glucan from oats
A study compared the Bifidobacteria levels in response (62). Beta-glucan induced the growth of Prevotella and Roseburia
to a randomized, double-blind, crossover trail. Participants with a concomitant increase in SCFA propionate production.
consumed both a standard enteral formula and a formula Inulin and all oligosaccharides had a strong bifidogenic effect
supplemented with fructooligiosaccharides (FOS) and fiber (59) (62). This study also showed that all natural sugars, most
as a sole source of nutrition for 14 days. FOS and fiber are notably non-digestible forms like inulin and oligosaccharides,
both forms of carbohydrates found naturally and abundantly in increase SCFA levels (62). The prebiotic effects differ due
plant foods–bananas, artichokes, onion, etc. While the volume of to the type of bacteria that each fiber is broken down by.
formula prescribed was based on individual energy expenditures, This is determined through bacterial specificity in which
a benchmark of 2,000 calories of the FOS/fiber formula provided specific gene clusters within the bacterial genome dictate the
10.2 g of FOS and 17.8 g of fiber. The average daily intake of saccharolytic enzymes that the bacteria can produce and,
fermentable non-digestible carbohydrates is estimated to be 10 g therefore, whether they can metabolize the prebiotic substrate
from inulin and FOS (60). This amount does not include meals (63). Non-digestible carbohydrates not only act as prebiotics by
and products supplemented with inulin and FOS, which typically promoting the growth of beneficial microorganisms, but also
add an additional 3–10 g/portion. Therefore, 10.2 g of FOS in the reduce proinflammatory cytokine production, concentrations
formula is realistic for human consumption. 17.8 g of fiber in the of serum triglycerides, total cholesterol, and LDL-cholesterol
formula is also realistic for human consumption as the average (54). Thus, non-digestible carbohydrates might confer protective
US male and female intake is 18 g and 15 g, respectively 1 . effects against cardiovascular disease and central nervous
Bifidobacterium is a butyrate-producing genus known to play system disorders.
a protective role in the human gut barrier by providing defense
against pathogens and diseases. When participants were given Proteins
formulas with FOS and fiber, their Bifidobacteria increased A majority of the studies have noted that protein consumption
from 5.1 to 26.6% (P = 0.003) after 14 days. When formula correlates positively with microbial diversity (54). However,
was given without FOS and fiber, Bifidobacteria only increased animal and plant-proteins influence the gut microbiota in
from 3.3 to 8.6% (P = 0.073). A negative correlation between different ways. For instance, individuals consuming a high
baseline Bifidobacteria and magnitude of the bifidogenic effect animal protein diet, from beef which is also high in fat,
was observed, indicating that those with lower initial amounts displayed lower abundances of bacteria, such as Roseburia,
of Bifidobacteria benefit most from fructooligiosaccharides and Eubacterium rectale, and Ruminococcus bromii, that metabolize
fiber intake. In contrast, high consumption of cholesterol from dietary plant polysaccharides (51). Populations of bacteria that
animal products, was strongly associated with a lower abundance increase in response to a high animal protein diet when
of Bifidobacteria (adj. p = 0.008). compared to subjects consuming a meatless diet are typically bile-
While these studies suggest that Bifidobacterium increase in tolerant microorganisms, such as Bacteroides and Clostridia (64).
response to a fiber-rich, high carbohydrate diet, other studies Additionally, a high-protein diet typically limits carbohydrate
have shown conflicting results. One important confounding intake, which may lead to a decrease in butyrate-producing
factor may be alcohol intake, which has been strongly bacteria, and thereby to a proinflammatory state and an increased
associated with a lower abundance of Bifidobacteria (adj. p = risk of colorectal cancer (65).
Individuals consuming pea protein exhibit increases in
1 https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/dbrief/ beneficial Bifidobacterium and Lactobacillus and decreases in
12_fiber_intake_0910.pdf. (Accessed February 12, 2019) pathogenic Bacteroides fragilis and Clostridium perfringens and,

Frontiers in Nutrition | www.frontiersin.org 5 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

consequently increases in intestinal SCFA levels (54). Likewise, synthesized post-translationally modified peptides etc.), but
plant-derived proteins have been associated with lower mortality here we would like to describe a few examples of well-
than animal-derived proteins (54). known diet-dependent metabolites, such as SCFA and others.
Depending on the bacteria and location along the intestinal
Fats tract, different bioactive molecules can be produced from
Current evidence suggests that both the quantity and the different prebiotics and nutrients (70, 73). Microbial metabolites
quality of consumed fat significantly impact the gut microbiota can have diverse positive health effects including local anti-
composition (65). inflammatory and immunomodulatory effects, and systemic
A plant-based diet is generally naturally low in fat, which anti-obesogenic, antihypertensive, hypocholesterolemic, anti-
favors beneficial Bifidobacteria in human gut microbiota. The proliferative, and antioxidant effects (74). These postbiotic effects
fat that does come from a vegan/vegetarian diet is made up of result from modulation of gene expression, metabolism, and
predominantly mono and polyunsaturated fats, which increase intestinal functioning and depend on microbiota composition
the Bacteroidetes:Firmicutes ratio, and on the genera level, and substrates, largely dependent on diet.
increase lactic acid bacteria, Bifidobacteria and Akkermansia
muciniphila (54). Nuts, particularly walnuts, have been shown Short-Chain Fatty Acids
to improve the gut microbiota by increasing Ruminococcaceae SCFAs act as a substrate to maintain colonic epithelium, and are
and Bifidobacteria, and decreasing Clostridium sp. cluster XIVa correlated with plant based food consumption (56). Maintenance
species (38). of the intestinal barrier prevents endotoxemia and the subsequent
On the other hand, saturated fat, found almost exclusively inflammatory effects (75, 76). SCFAs acetate, propionate, and
in animal sources, increases Bilophila and Faecalibacterium butyrate, are mostly microbial metabolites of fermented fiber
prausnitzii, and decreases Bifidobacterium (54). Some studies and other carbohydrates, although a small fraction can derive
report that this change activates inflammation (induces pro- from proteins. The fecal levels of these metabolites (and the
inflammatory cytokines such as IL-1, IL-6, and TNF-α) and corresponding esters) positively correlate with the consumption
leads to metabolic disorders (66). High consumption of saturated of fruits, vegetables, and legumes. Thus, their levels significantly
and trans fat, predominately found in a Western diet, increases increase in people who begin a plant-based diet. Interestingly,
the risk of cardiovascular disease and reduces Bacteroidetes, an increase in SCFAs is observed when omnivores consume a
Bacteroides, Prevotella, Lactobacillus ssp. and Bifidobacterium Mediterranean diet rich in fruit, legumes and vegetables (77).
spp, and increases Firmicutes (40, 67). While specific gut microbes are predisposed for SCFA
N-3 polyunsaturated fatty acids, have been found to result production, different bacteria are known to produce different
in either no change to the microbiota, or beneficial increases SCFAs. For example, enteric bacteria, such as Akkermansia
in Bifidobacterium, Adlercreutzia, Lactobacillus, Streptococcus, muciniphila, Bifidobacterium spp., Prevotella spp., and
Desulfovibrio, and Verrucomicrobia (Akkermansia muciniphila) Bacteroides spp. produce acetate; Bacteroides spp. produce
(54, 67). propionate; and Coprococcus produces butyrate (78). The
most butyrate producing bacteria are in Clostridium Cluster
Polyphenols XIVa, IV, and XVI. These species are positively correlated with
Polyphenols, or naturally occurring plant metabolites (68), consumption of plant foods, and produce SCFAs that yield
in plant foods increase Bifidobacterium and Lactobacillus several health benefits.
abundance, which provide anti-pathogenic and anti- The protective role of acetate, propionate and butyrate against
inflammatory effects and cardiovascular protection (54). different types of disease, such as type 2 diabetes, inflammatory
Common polyphenol-rich foods include fruits, seeds, vegetables, bowel disease, and immune diseases, is well documented. For
tea, cocoa products, and wine. For example, polyphenol example, it has been shown that SCFAs promote immunity
extracts from tea generate an increase in Bifidobacterium and against pathogens (78), and are important components for
Lactobacillus–Enterococcus spp., which then yields an increased microglia function and maturation and control of the blood–
SCFA production on human microbiota in vitro (69). brain barrier integrity (79). Other effect of SCFAs is to increase
thermogenesis, preventing/treating obesity (80, 81). SCFAs serve
INFLUENCE OF MICROBIOME as energy substrates for colonocytes, as well as for the body
POSTBIOTICS ON HUMAN HEALTH generally. For example, propionate serves as a gluconeogenic
substrate in the liver and in the intestine (78).
Research on the gut-brain, gut-lung, and gut-liver axes Microbial interactions with dietary polysaccharides and the
highlights the importance of the microbiome on systemic resulting SCFAs are important energy and signaling molecules.
human health. Studies note changes in central neural chemistry, It is becoming increasingly accepted that butyrate-producing
inflammatory lung conditions, and non-alcoholic fatty liver bacteria and butyrate, per se, may be beneficial for human health
disease pathogenesis with changes to microbial composition (78). Butyrate has been shown to play a key role in gut physiology
(70–72). The mechanism of communication among these as a major carbon source for colonocytes. It helps regulate critical
organs stems from the microbial products and microbial functions of the intestine, such as intestinal motility, mucus
metabolites of ingested nutrients. These products can be production, visceral sensitivity, the epithelial barrier, immune
diet-independent (such as lipopolysaccharides, ribosomally homeostasis, and the mucosal oxygen gradient (82, 83). Thus,

Frontiers in Nutrition | www.frontiersin.org 6 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

dietary fiber and carbohydrates can affect SCFA degradation relating toneoplastic, atherosclerotic, and neurodegenerative
while altering the abundance of the associated microbes. Taking processes (25).
together, diets rich in fiber might provide benefits to the intestine,
as well as overall health. Aryl-Hydrocarbon Receptor Ligands
Intestinal aryl-hydrocarbon receptor ligands are predominantly
Phytoestrogens diet derived from plant food, specifically cruciferous vegetables.
Phytoestrogens are plant-derived polyphenols that interact with Through aryl-hydrocarbon receptors, the ligands act to promote
estrogen receptors with either agonist or antagonist actions. A intestinal immune function and gut homeostasis (95). Since aryl-
large majority of polyphenols are delivered to the gut, given hydrocarbon receptor ligands are gut microbiota-derived, any
their 1% bioavailability (57). The protective effects of plant impairment to the gut microbiota, such as from a high-fat diet,
polyphenols, particularly their anti-cancer, anti-inflammatory, can decrease aryl-hydrocarbon receptor ligands. In turn, this
and antioxidant effects, and their association with decreased can cause gut inflammation and permeability and promote the
risks of cardiovascular disease, obesity, diabetes, osteoporosis, development of metabolic syndrome, which can be improved by
and amyloid formation have been observed in humans (84–86). supplementation with a Lactobacillus strain (96). Additionally, a
Increasing evidence shows that these effects are reached after decrease in aryl-hydrocarbon receptors or ligands compromises
bioactivation of the polyphenols by the gut microbiota (87, 88). the maintenance of intraepithelial lymphocytes and the control
Even though plant polyphenols have protective effects on human of the microbial load and composition, resulting in heightened
health, especially in the bioactive form, there is still a possibility immune activation and epithelial damage (95).
of adverse effects due to their complexity of action and potential
inter-individual variability (89). Secondary Bile Acids and Coprostanol
While not all types of microbes participating in polyphenol A separate group of postbiotics are cholesterol metabolites.
metabolism are yet known, it has recently been shown that Several bacterial strains, isolated from intestine or feces, are
Bifidobacterium, Lactobacillus sp., Coriobacteriaceae, Clostridium described to convert dietary or synthesized de novo cholesterol
sp., Bacteroides, and Saccharomyces yeast, are involved in into coprostanol (97, 98), which is poorly absorbed by the
the process of converting polyphenols to equol, urolithins, human intestine. Thus, serum cholesterol in host is reduced,
and enterolignans (74, 88). The qualitative and quantitative which decreases the risk of cardiovascular diseases. On the other
proportions of urolithins and equol produced correlate positively hand, bile acids synthetized from cholesterol are converted by
with the effects of phytoestrogens (88). Other bacterial species, microbiota into secondary bile acids, found in different tissues
such as Coriobacteriaceae and Eubacterium, are responsible for and in feces. It is believed secondary bile acids are involved
different polyphenol transformations (88). in the equilibrium of health/disease (73, 97). For example,
The interaction of polyphenols and gut microbiota is they are associated with inflammatory bowel disease, liver and
bidirectional (90, 91). The gut bacteria produce microbial colon cancer.
metabolites from polyphenols, which in turn serve as prebiotics
for the gut bacteria. These metabolites, particularly urolithins, Trimethylamine N-Oxide (TMAO)
promote the growth of Lactobacillus and Bifidobacterium(88). Trimethylamine N-Oxide is a microbial metabolite believed to
be associated with cardiovascular and neurological disorders.
Carnitine and choline are the precursors of TMAO and are
Vitamins primarily found in foods of animal origin (eggs, beef, pork),
Gut microbiota are crucial for adequate vitamin levels in the with lower amounts found in beans and fish (99). Several
human body. Menaquinone, folate, cobalamin, and riboflavin microbial genera, like L-Ruminococcus, have been linked to the
(ie: vitamins K, B9, and B2) are produced by gut microbes intake of animal proteins and fat and have been associated with
(25). Different bacteria have biosynthetic properties for different TMAO levels (77). In general, meat intake appears to proliferate
vitamins, such as Bifidobacterium for vitamins K, B12 , biotin, species of Bacteroides, Alistipes, Ruminococcus, Clostridia, and
folate, thiamine, Bacillus subtilis and Escherichia coli for Bilophila, and decease Bifidobacterium. Higher TMAO levels
riboflavin (92), and Lactobacillus for cobalamin and other have also been observed with red meat intake, increasing risk
B vitamins (93). The pathway analysis of the predicted for cardiovascular disease and inflammatory bowel disease (54,
metagenomes showed an enrichment of folate biosynthesis in 66). Vegetarians have a different gut microbiota composition
vegans compared with omnivores (77). than omnivores with a diminished capacity to produce
trimethylamine (TMA), the precursor to TMAO. The plasma
Isothiocyanates concentrations of TMAO appear to be similar in vegans and
Isothiocyanates are compounds from glucosinolates, mainly lacto-ovo-vegetarians (99, 100).
found in plants, like cruciferous vegetables. Escherichia coli, Lowering TMAO levels may be achieved through greater
certain Bacteroides, some Enterococcus, Lactobacillus agilis, adherence to the Mediterranean diet, particularly a vegetarian
certain Peptostreptococcus spp. and Bifidobacterium spp. one rich in fruits and vegetables (77, 100). Increased vegetable
metabolize glucosinolates to isothiocyanates, secreting their own consumption reduces TMAO levels by reducing the enzymes
myrosinase enzyme (94). These metabolites have cytoprotective responsible for converting TMA to TMAO and by remodeling
and anti-oxidative effects through regulation of gene expression the gut microbiota. The studies have shown TMAO production

Frontiers in Nutrition | www.frontiersin.org 7 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

to decrease in vegetarians, which decreases their cardiovascular crucial for metabolizing nutrients into active for the host
risk. To be objective, we have to mention a recent study, postbiotics. Up to date knowledge suggests that a plant-
leaving a room for further analyses. Vegan fecal microbiota based diet may be an effective way to promote a diverse
transplantation in metabolic syndrome patients resulted in ecosystem of beneficial microbes that support overall
significant changes in intestinal microbiota composition but health. Nonetheless, due to the complexity and inter-
failed to show changes in TMAO production. Authors explained individual differences, further research is required to fully
that the 2-week follow-up was not a sufficient length of time to characterize the interactions between diet, the microbiome, and
observe changes in TMAO production (101). health outcomes.
On average, twenty five percent of plasma metabolites are
different between omnivores and vegans, suggesting a significant AUTHOR CONTRIBUTIONS
direct effect of diet on the host metabolome. No unique
bacterial taxa have been significantly associated with individual AT and IB contributed to conception and writing of the
metabolite levels after adjustment for multiple comparisons manuscript, ER, WY, JA, NB, and HK contributed and
(102). These findings suggest that while inter-individual critically revised the manuscript. All authors approved the
variability exists, dietary patterns significantly influence the final manuscript.
microbial composition.
FUNDING
CONCLUSION
This work was funded by PCRM and supported by the Grant
Current research indicates that diet is the essential factor Agency of Ministry of Education, Science, Research and Sport of
for human gut microbiota composition, what in its turn is the Slovak Republic VEGA 1/0286/18.

REFERENCES 12. Spor A, Koren O, Ley R. Unravelling the effects of the environment and
host genotype on the gut microbiome. Nat Rev Microbiol. (2011) 9:279–90.
1. Sender R, Fuchs S, Milo R. Revised estimates for the number of doi: 10.1038/nrmicro2540
human and bacteria cells in the body. PLoS Biol. (2016) 14:e1002533. 13. Jiang C, Li G, Huang P, Liu Z, Zhao B. The gut microbiota and Alzheimer’s
doi: 10.1371/journal.pbio.1002533 Disease. J Alzheimers Dis JAD. (2017) 58:1–15. doi: 10.3233/JAD-161141
2. Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh 14. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann
C, et al. A human gut microbial gene catalogue established by J, et al. Short chain fatty acids and gut microbiota differ between patients with
metagenomic sequencing. Nature. (2010) 464:59–65. doi: 10.1038/nature Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord.
08821 (2016) 32:66–72. doi: 10.1016/j.parkreldis.2016.08.019
3. Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, et al. The 15. Ding HT, Taur Y, Walkup JT. Gut microbiota and autism: key
complete genome of an individual by massively parallel DNA sequencing. concepts and findings. J Autism Dev Disord. (2017) 47:480–9.
Nature. (2008) 452:872–6. doi: 10.1038/nature06884 doi: 10.1007/s10803-016-2960-9
4. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley 16. Jonsson AL, Bäckhed F. Role of gut microbiota in atherosclerosis. Nat Rev
RE, et al. A core gut microbiome in obese and lean twins. Nature. (2009) Cardiol. (2017) 14:79–87. doi: 10.1038/nrcardio.2016.183
457:480–4. doi: 10.1038/nature07540 17. Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, et al.
5. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, Gastrointestinal microbiota in children with autism in Slovakia. Physiol
et al. Enterotypes of the human gut microbiome. Nature. (2011) 473:174–80. Behav. (2015) 138:179–87. doi: 10.1016/j.physbeh.2014.10.033
doi: 10.1038/nature09944 18. Selber-Hnatiw S, Rukundo B, Ahmadi M, Akoubi H, Al-Bizri H, Aliu AF,
6. Roager HM, Licht TR, Poulsen SK, Larsen TM, Bahl MI. Microbial et al. Human gut microbiota: toward an ecology of disease. Front Microbiol.
enterotypes, inferred by the prevotella-to-bacteroides ratio, remained (2017) 8:1265. doi: 10.3389/fmicb.2017.01265
stable during a 6-month randomized controlled diet intervention 19. Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of
with the new nordic diet. Appl Environ Microbiol. (2014) 80:1142–9. human metabolism. Nature. (2016) 535:56–64. doi: 10.1038/nature18846
doi: 10.1128/AEM.03549-13 20. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al.
7. Bull MJ, Plummer NT. Part 1: The human gut microbiome in health and Linking long-term dietary patterns with gut microbial enterotypes. Science.
disease. Integr Med Clin J. (2014) 13:17–22. (2011) 334:105–8. doi: 10.1126/science.1208344
8. Neish AS. Microbes in gastrointestinal health and disease. 21. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome.
Gastroenterology. (2009) 136:65–80. doi: 10.1053/j.gastro.2008. Genome Med. (2016) 8:51. doi: 10.1186/s13073-016-0307-y
10.080 22. Yan W, Zheng J, Wen C, Ji C, Zhang D, Chen Y, et al. Efficacy of fecal
9. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human sampling as a gut proxy in the study of chicken gut microbiota. bioRxiv.
gut microbes associated with obesity. Nature. (2006) 444:1022–3. 2018:313577. doi: 10.1101/313577
doi: 10.1038/4441022a 23. Glick-Bauer M, Yeh MC. The health advantage of a vegan diet:
10. Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen exploring the gut microbiota connection. Nutrients. (2014) 6:4822–38.
AS, Pedersen BK, et al. Gut microbiota in human adults with type doi: 10.3390/nu6114822
2 diabetes differs from non-diabetic adults. PLoS ONE. (2010) 5:e9085. 24. Salonen A, de Vos WM. Impact of diet on human intestinal
doi: 10.1371/journal.pone.0009085 microbiota and health. Annu Rev Food Sci Technol. (2014) 5:239–62.
11. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune doi: 10.1146/annurev-food-030212-182554
responses during health and disease. Nat Rev Immunol. (2009) 9:313–23. 25. Derrien M, Veiga P. Rethinking diet to aid human-microbe symbiosis.
doi: 10.1038/nri2515 Trends Microbiol. (2017) 25:100–12. doi: 10.1016/j.tim.2016.09.011

Frontiers in Nutrition | www.frontiersin.org 8 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

26. Wong MW, Yi CH, Liu TT, Lei WY, Hung JS, Lin CL, et al. Impact of vegan health in the elderly. Nature. (2012) 488:178–84. doi: 10.1038/nature
diets on gut microbiota: an update on the clinical implications. Tzu Chi Med 11319
J. (2018) 30:200–3. doi: 10.4103/tcmj.tcmj_21_18 47. Ruengsomwong S, La-Ongkham O, Jiang J, Wannissorn B, Nakayama
27. Klimenko NS, Tyakht AV, Popenko AS, Vasiliev AS, Altukhov IA, Ischenko J, Nitisinprasert S. Microbial community of healthy thai vegetarians
DS, et al. Microbiome responses to an uncontrolled short-term diet and non-vegetarians, their core gut microbiota, and pathogen risk.
intervention in the frame of the citizen science project. Nutrients. (2018) J Microbiol Biotechnol. (2016) 26:1723–35. doi: 10.4014/jmb.1603.
10:E576. doi: 10.3390/nu10050576 03057
28. Martínez I, Lattimer JM, Hubach KL, Case JA, Yang J, Weber CG, et al. Gut 48. Jeffery IB, O’Toole PW. Diet-microbiota interactions and their implications
microbiome composition is linked to whole grain-induced immunological for healthy living. Nutrients. (2013) 5:234–252. doi: 10.3390/nu5010234
improvements. ISME J. (2013) 7:269–80. doi: 10.1038/ismej.2012.104 49. Matijašić BB, Obermajer T, Lipoglavšek L, Grabnar I, Avguštin
29. Zimmer J, Lange B, Frick JS, Sauer H, Zimmermann K, Schwiertz A, et al. G, Rogelj I. Association of dietary type with fecal microbiota in
A vegan or vegetarian diet substantially alters the human colonic faecal vegetarians and omnivores in Slovenia. Eur J Nutr. (2014) 53:1051–64.
microbiota. Eur J Clin Nutr. (2012) 66:53–60. doi: 10.1038/ejcn.2011.141 doi: 10.1007/s00394-013-0607-6
30. Scott KP, Duncan SH, Flint HJ. Dietary fibre and the gut microbiota. Nutr 50. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T,
Bull. (2008). 33: 201–211. doi: 10.1111/j.1467-3010.2008.00706.x et al. Dietary fiber-induced improvement in glucose metabolism is associated
31. Verdam FJ, Fuentes S, de Jonge C, Zoetendal EG, Erbil R, Greve JW, with increased abundance of prevotella. Cell Metab. (2015) 22:971–82.
et al. Human intestinal microbiota composition is associated with local and doi: 10.1016/j.cmet.2015.10.001
systemic inflammation in obesity. Obes Silver Spring Md. (2013) 21:E607– 51. David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE,
615. doi: 10.1002/oby.20466 Wolfe BE, et al. Diet rapidly and reproducibly alters the human
32. Orlich MJ, Fraser GE. Vegetarian diets in the Adventist Health Study gut microbiome. Nature. (2014) 505:559–63. doi: 10.1038/nature
2: a review of initial published findings1234. Am J Clin Nutr. 12820
(2014) 100:353S−8S. doi: 10.3945/ajcn.113.071233 52. Whisner CM, Maldonado J, Dente B, Krajmalnik-Brown R, Bruening M.
33. Menni C, Lin C, Cecelja M, Mangino M, Matey-Hernandez ML, Keehn L, Diet, physical activity and screen time but not body mass index are associated
et al. Gut microbial diversity is associated with lower arterial stiffness in with the gut microbiome of a diverse cohort of college students living in
women. Eur Heart J. (2018) 39:2390–7. doi: 10.1093/eurheartj/ehy226 university housing: a cross-sectional study. BMC Microbiol. (2018) 18:210.
34. Rizzoni D, Porteri E, Guelfi D, Muiesan ML, Valentini U, Cimino A, doi: 10.1186/s12866-018-1362-x
et al. Structural alterations in subcutaneous small arteries of normotensive 53. Ishii C, Nakanishi Y, Murakami S, Nozu R, Ueno M, Hioki K,
and hypertensive patients with non-insulin-dependent diabetes mellitus. et al. A metabologenomic approach reveals changes in the intestinal
Circulation. (2001) 103:1238–44. doi: 10.1161/01.CIR.103.9.1238 environment of mice fed on american diet. Int J Mol Sci. (2018) 19:E4079.
35. Losasso C, Eckert EM, Mastrorilli E, Villiger J, Mancin M, Patuzzi I, et al. doi: 10.3390/ijms19124079
Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented 54. Singh RK, Chang H-W, Yan D, Lee KM, Ucmak D, Wong K, et al. Influence
Westernized Dietary Styles on Human gut microbiota: a cross sectional of diet on the gut microbiome and implications for human health. J Transl
study. Front Microbiol. (2018) 9:317. doi: 10.3389/fmicb.2018.00317 Med. (2017) 15:73. doi: 10.1186/s12967-017-1175-y
36. do Rosario VA, Fernandes R, Trindade EB. Vegetarian diets and gut 55. Moschen AR, Wieser V, Tilg H. Dietary factors: major regulators of
microbiota: important shifts in markers of metabolism and cardiovascular the Gut’s microbiota. Gut Liver. (2012) 6:411–6. doi: 10.5009/gnl.2012.
disease. Nutr Rev. (2016) 74:444–54. doi: 10.1093/nutrit/nuw012 6.4.411
37. Simpson HL, Campbell BJ. Review article: dietary fibre- 56. Zhang C, Björkman A, Cai K, Liu G, Wang C, Li Y, et al. Impact of a 3-
microbiota interactions. Aliment Pharmacol Ther. (2015) 42:158–79. months vegetarian diet on the gut microbiota and immune repertoire. Front
doi: 10.1111/apt.13248 Immunol. (2018) 9:908. doi: 10.3389/fimmu.2018.00908
38. Bamberger C, Rossmeier A, Lechner K, Wu L, Waldmann E, Fischer 57. Ercolini D, Fogliano V. Food design to feed the human gut microbiota. J Agric
S, et al. A walnut-enriched diet affects gut microbiome in healthy Food Chem. (2018) 66:3754–8. doi: 10.1021/acs.jafc.8b00456
caucasian subjects: a randomized, controlled trial. Nutrients. (2018) 10. 58. Zinöcker MK, Lindseth IA. The western diet-microbiome-host
doi: 10.3390/nu10020244 interaction and its role in metabolic disease. Nutrients. (2018) 10:3.
39. Jain A, Li XH, Chen WN. Similarities and differences in gut microbiome doi: 10.3390/nu10030365
composition correlate with dietary patterns of Indian and Chinese adults. 59. Whelan K, Judd PA, Preedy VR, Simmering R, Jann A, Taylor MA.
AMB Express. (2018) 8:104. doi: 10.1186/s13568-018-0632-1 Fructooligosaccharides and fiber partially prevent the alterations in
40. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart fecal microbiota and short-chain fatty acid concentrations caused by
S, et al. Impact of diet in shaping gut microbiota revealed by a comparative standard enteral formula in healthy humans. J Nutr. (2005) 135:1896–902.
study in children from Europe and rural Africa. Proc Natl Acad Sci USA. doi: 10.1093/jn/135.8.1896
(2010) 107:14691–6. doi: 10.1073/pnas.1005963107 60. Ten Bruggencate SJ, Bovee-Oudenhoven IM, Lettink-Wissink ML, Katan
41. Martínez I, Kim J, Duffy PR, Schlegel VL, Walter J. Resistant starches MB, van der Meer R. Dietary fructooligosaccharides affect intestinal barrier
types 2 and 4 have differential effects on the composition of the function in healthy men. J Nutr. (2006) 136:70–4. doi: 10.1093/jn/136.1.70
fecal microbiota in human subjects. PloS ONE. (2010) 5:e15046. 61. Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-
doi: 10.1371/journal.pone.0015046 utilizing capacity varies in Prevotella- versus Bacteroides-dominated
42. Ley RE, Bäckhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon gut microbiota. Sci Rep. (2017) 7:2594. doi: 10.1038/s41598-017-0
JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA. (2005) 2995-4
102:11070–5. doi: 10.1073/pnas.0504978102 62. Fehlbaum S, Prudence K, Kieboom J, Heerikhuisen M, van den Broek T,
43. Lin A, Bik EM, Costello EK, Dethlefsen L, Haque R, Relman DA, et al. Schuren FHJ, et al. In vitro fermentation of selected prebiotics and their
Distinct distal gut microbiome diversity and composition in healthy children effects on the composition and activity of the adult gut microbiota. Int J Mol
from Bangladesh and the United States. PloS ONE. (2013) 8:e53838. Sci. (2018) 19:10. doi: 10.3390/ijms19103097
doi: 10.1371/journal.pone.0053838 63. Wilson B, Whelan K. Prebiotic inulin-type fructans and galacto-
44. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, et al. Microbiota oligosaccharides: definition, specificity, function, and application in
and SCFA in lean and overweight healthy subjects. Obes Silver Spring Md. gastrointestinal disorders. J Gastroenterol Hepatol. (2017) 32:64–8.
(2010) 18:190–5. doi: 10.1038/oby.2009.167 doi: 10.1111/jgh.13700
45. Andoh A, Nishida A, Takahashi K, Inatomi O, Imaeda H, Bamba S, et al. 64. Hentges DJ, Maier BR, Burton GC, Flynn MA, Tsutakawa RK. Effect
Comparison of the gut microbial community between obese and lean peoples of a high-beef diet on the fecal bacterial flora of humans. Cancer Res.
using 16S gene sequencing in a Japanese population. J Clin Biochem Nutr. (1977) 37:568–71.
(2016) 59:65–70. doi: 10.3164/jcbn.15-152 65. Sheflin AM, Melby CL, Carbonero F, Weir TL. Linking dietary patterns with
46. Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, Cusack gut microbial composition and function. Gut Microbes. (2016) 8:113–29.
S, et al. Gut microbiota composition correlates with diet and doi: 10.1080/19490976.2016.1270809

Frontiers in Nutrition | www.frontiersin.org 9 April 2019 | Volume 6 | Article 47

Tomova et al. Diet Impact on Gut Microbiota

66. Lee YK. Effects of diet on gut microbiota profile and the implications 87. Landete JM, Arqués J, Medina M, Gaya P, de Las Rivas B, Muñoz R.
for health and disease. Biosci Microbiota Food Health. (2013) 32:1–12. Bioactivation of phytoestrogens: intestinal bacteria and health. Crit Rev Food
doi: 10.12938/bmfh.32.1 Sci Nutr. (2016) 56:1826–43. doi: 10.1080/10408398.2013.789823
67. Coelho OGL, Cândido FG, Alfenas RCG. Dietary fat and gut microbiota: 88. Tomás-Barberán FA, González-Sarrías A, García-Villalba R, Núñez-Sánchez
mechanisms involved in obesity control. Crit Rev Food Sci Nutr. (2018) MA, Selma MV, García-Conesa MT, et al. Urolithins, the rescue of “old”
2018:1–9. doi: 10.1080/10408398.2018.1481821 metabolites to understand a “new” concept: Metabotypes as a nexus among
68. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in phenolic metabolism, microbiota dysbiosis, and host health status. Mol Nutr
human health and disease. Oxid Med Cell Longev. (2009) 2:270–8. Food Res. (2017) 61:1. doi: 10.1002/mnfr.201500901
doi: 10.4161/oxim.2.5.9498 89. Rietjens IMCM, Louisse J, Beekmann K. The potential health effects
69. Sun H, Chen Y, Cheng M, Zhang X, Zheng X, Zhang Z. The modulatory of dietary phytoestrogens. Br J Pharmacol. (2017) 174:1263–80.
effect of polyphenols from green tea, oolong tea and black tea on human doi: 10.1111/bph.13622
intestinal microbiota in vitro. J Food Sci Technol. (2018) 55:399–407. 90. Cardona F, Andrés-Lacueva C, Tulipani S, Tinahones FJ, Queipo-Ortuño MI.
doi: 10.1007/s13197-017-2951-7 Benefits of polyphenols on gut microbiota and implications in human health.
70. Klemashevich C, Wu C, Howsmon D, Alaniz RC, Lee K, Jayaraman J Nutr Biochem. (2013) 24:1415–22. doi: 10.1016/j.jnutbio.2013.05.001
A. Rational identification of diet-derived postbiotics for improving 91. Ozdal T, Sela DA, Xiao J, Boyacioglu D, Chen F, Capanoglu E. The
intestinal microbiota function. Curr Opin Biotechnol. (2014) 26:85–90. reciprocal interactions between polyphenols and gut microbiota and effects
doi: 10.1016/j.copbio.2013.10.006 on bioaccessibility. Nutrients. (2016) 8:2. doi: 10.3390/nu8020078
71. Cryan JF, O’Mahony SM. The microbiome-gut-brain axis: from 92. De Filippis F, Pellegrini N, Laghi L, Gobbetti M, Ercolini D. Unusual sub-
bowel to behavior. Neurogastroenterol Motil. (2011) 23:187–92. genus associations of faecal Prevotella and Bacteroides with specific dietary
doi: 10.1111/j.1365-2982.2010.01664.x patterns. Microbiome. (2016) 4. doi: 10.1186/s40168-016-0202-1
72. Compare D, Coccoli P, Rocco A, Nardone OM, De Maria S, Cartenì 93. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M.
M, et al. Gut–liver axis: The impact of gut microbiota on non- Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr
alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis. (2012) 22:471–6. Opin Biotechnol. (2013) 24:160–8. doi: 10.1016/j.copbio.2012.08.005
doi: 10.1016/j.numecd.2012.02.007 94. Tian S, Liu X, Lei P, Zhang X, Shan Y. Microbiota: a mediator to
73. Donia MS, Fischbach MA. Human microbiota. Small molecules transform glucosinolate precursors in cruciferous vegetables to the active
from the human microbiota. Science. (2015) 349:1254766. isothiocyanates. J Sci Food Agric. (2018) 98:1255–60. doi: 10.1002/jsfa.8654
doi: 10.1126/science.1254766 95. Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva
74. Aguilar-Toalá JE, Garcia-Varela R, Garcia HS, et al. Postbiotics: An evolving EF, et al. Exogenous stimuli maintain intraepithelial lymphocytes
term within the functional foods field. Trends Food Sci Technol. (2018) via aryl hydrocarbon receptor activation. Cell. (2011) 147:629–40.
75:105–14. doi: 10.1016/j.tifs.2018.03.009 doi: 10.1016/j.cell.2011.09.025
75. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut 96. Natividad JM, Lamas B, Pham HP, Michel ML, Rainteau D, Bridonneau
microbiota and their impact on human metabolism. Gut Microbes. (2016) C, et al. Bilophila wadsworthia aggravates high fat diet induced
7:189–200. doi: 10.1080/19490976.2015.1134082 metabolic dysfunctions in mice. Nat Commun. (2018) 9:2802.
76. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota doi: 10.1038/s41467-018-05249-7
control metabolic endotoxemia-induced inflammation in high-fat diet- 97. Gérard P. Metabolism of cholesterol and bile acids by the gut microbiota.
induced obesity and diabetes in mice. Diabetes. (2008) 57:1470–81. Pathogens. (2013) 3:14–24. doi: 10.3390/pathogens3010014
doi: 10.2337/db07-1403 98. Horáčková Š, Plocková M, Demnerová K. Importance of microbial defence
77. De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, systems to bile salts and mechanisms of serum cholesterol reduction.
et al. High-level adherence to a Mediterranean diet beneficially impacts Biotechnol Adv. (2018) 36:682–90. doi: 10.1016/j.biotechadv.2017.12.005
the gut microbiota and associated metabolome. Gut. (2016) 65:1812–21. 99. Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of
doi: 10.1136/gutjnl-2015-309957 trimethylamine N-Oxide (TMAO) in disease: potential biomarker or new
78. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber therapeutic target. Nutrients. (2018) 10:10. doi: 10.3390/nu10101398
to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 100. Obeid R, Awwad HM, Keller M, Geisel J. Trimethylamine-N-oxide and
(2016) 165:1332–45. doi: 10.1016/j.cell.2016.05.041 its biological variations in vegetarians. Eur J Nutr. (2017) 56:2599–609.
79. Erny D, Hrabě de Angelis AL, Prinz M. Communicating systems in the body: doi: 10.1007/s00394-016-1295-9
how microbiota and microglia cooperate. Immunology. (2017) 150:7–15. 101. Smits LP, Kootte RS, Levin E, Prodan A, Fuentes S, Zoetendal EG, et al.
doi: 10.1111/imm.12645 Effect of vegan fecal microbiota transplantation on carnitine- and choline-
80. Reynés B, Palou M, Rodríguez AM, Palou A. Regulation of adaptive derived trimethylamine-N-oxide production and vascular inflammation
thermogenesis and browning by prebiotics and postbiotics. Front Physiol. in patients with metabolic syndrome. J Am Heart Assoc. (2018) 7:7.
(2019) 9:1908. doi: 10.3389/fphys.2018.01908 doi: 10.1161/JAHA.117.008342
81. Canfora EE, Meex RCR, Venema K, Blaak EE. Gut microbial 102. Wu GD, Compher C, Chen EZ, Smith SA, Shah RD, Bittinger K, et al.
metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol. (2019). Comparative metabolomics in vegans and omnivores reveal constraints on
doi: 10.1038/s41574-019-0156-z diet-dependent gut microbiota metabolite production. Gut. (2016) 65:63–72.
82. Velázquez OC, Lederer HM, Rombeau JL. Butyrate and the colonocyte. doi: 10.1136/gutjnl-2014-308209
Production, absorption, metabolism, and therapeutic implications. Adv Exp 103. Hayashi H, Sakamoto M, Benno Y. Fecal microbial diversity in a strict
Med Biol. (1997) 427:123–34. doi: 10.1007/978-1-4615-5967-2_14 vegetarian as determined by molecular analysis and cultivation. Microbiol
83. Borycka-Kiciak K, Banasiewicz T, Rydzewska G. Butyric acid – a Immunol. (2002) 46:819–31. doi: 10.1111/j.1348-0421.2002.tb02769.x
well-known molecule revisited. Przeglad Gastroenterol. (2017) 12:83–9.
doi: 10.5114/pg.2017.68342 Conflict of Interest Statement: The authors declare that the research was
84. Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci. conducted in the absence of any commercial or financial relationships that could
(2016) 5:e47, 1–15. doi: 10.1017/jns.2016.41 be construed as a potential conflict of interest.
85. Ono K, Li L, Takamura Y, Yoshiike Y, Zhu L, Han F, et al. Phenolic
compounds prevent amyloid β-protein oligomerization and synaptic Copyright © 2019 Tomova, Bukovsky, Rembert, Yonas, Alwarith, Barnard and
dysfunction by site-specific binding. J Biol Chem. (2012) 287:14631–43. Kahleova. This is an open-access article distributed under the terms of the Creative
doi: 10.1074/jbc.M111.325456 Commons Attribution License (CC BY). The use, distribution or reproduction in
86. Hossen MS, Ali MY, Jahurul MHA, Abdel-Daim MM, Gan SH, other forums is permitted, provided the original author(s) and the copyright owner(s)
Khalil MI. Beneficial roles of honey polyphenols against some human are credited and that the original publication in this journal is cited, in accordance
degenerative diseases: a review. Pharmacol Rep. (2017) 69:1194–205. with accepted academic practice. No use, distribution or reproduction is permitted
doi: 10.1016/j.pharep.2017.07.002 which does not comply with these terms.

Frontiers in Nutrition | www.frontiersin.org 10 April 2019 | Volume 6 | Article 47