R: Concise Reviews

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Diet Effects in Gut Microbiome and Obesity

Jia Chen, Xianzhi He, and Jinhai Huang

Abstract: The 100 trillion microbes in human gut coevolve with the host and exert significant influences on human
health. The gut microbial composition presents dynamic changes correlated with various factors including host genotypes,
age, and external environment. Effective manipulation of the gut microbiota through diets (both long-term and shortterm diet patterns), probiotics and/or prebiotics, and antibiotics has been proved being potential to prevent from metabolic
disorders such as obesity in many studies. The dietary regulation exerts influences on microbial metabolism and host
immune functions through several pathways, of which may include selectively bacterial fermentation of nutrients, lower
intestinal barrier function, overexpression of genes associated with disorders, and disruptions to both innate and adaptive
immunity. Discoveries in the interrelationship between diet, intestinal microbiome, and body immune system provide
us novel perceptions to the specific action mechanisms and will promote the development of therapeutic approaches for
obesity.
Keywords: diet, gut microbiota, obesity, prebiotic

Introduction
Our human gut is colonized with a complex community of
100 trillion microbe cells, which is 10-fold the number of eukaryotic cells in the human body, and it is estimated that they
represent 150 times unique genes than our own genome. Cultureindependent methods such as 16S ribosomal RNA analysis revealed that the adult microbiota is rich in the level of bacterial
species (1000 to 1150 species; Qin and others 2010) but limited
in the phylotypes of which mainly are Firmicutes and Bacteroidetes,
constitute over 90% of the gut bacteria cells (Ley and others 2006a,
2006b; Turnbaugh and Gordon 2009).
The microbiota (commensal and symbiotic microbes reside in
our guts) varies between individuals but studies of microbiome
(microbial metagenome sequences) have demonstrated that the
functional gene repertoires exhibit great similarity among individuals especially adults (Turnbaugh and others 2009c).The composition of gut microbiota within an individual is inherently
associated with host genotypes and age and moreover presents dynamic changes affected by external factors such as diets, antibiotics,
and prebiotics and probiotics, which may result in dysbacteriosis
(Figure 1).
Accumulating evidence indicates that a dysfunctional microecosystem (such as a decrease in microbial diversity) may relate to
enteral inflammation such as inflammatory bowel disease (IBD;
Macfarlane 2009) and several extra-intestinal diseases such as obesity (Ley and others 2005; Turnbaugh and others 2006), diabetes
(Creely and others 2007; Cani and others 2008), liver disease (Brun
and others 2007; Yin and others 2010), cardiometabolic complications (Shen and others 2013), and even cancer (Scanlan and others
2008; Tlaskalova-Hogenova and others 2011). Thus, making clear
the mechanisms of gut microbiota acting on host metabolism and
regulating the microbial composition through diets, prebiotics and
probiotics, and antibiotics exerts significant influences on human
health.
The dietary regulation exerts influences on microbial
metabolism and host immune functions through several pathways

of which may include selectively bacterial fermentation of nutrients, lower intestinal barrier function, overexpression of genes
associated with disorders, and disruptions to intestinal function by
causing both innate- and adaptive-immune responses (Kau and
others 2011; Shulzhenko and others 2011). The majority of gut
microbes play as crucial vehicles in the host metabolism by improving energy harvest from foods, for example they are able to degrade
the polysaccharide that is indigestible to the host. Besides they can
improve mucosal immunity, intestinal permeability, and modulate
the host-derived compounds, thus having a profound effects on
human life (Hooper and others 2002; Ley and others 2005).
Better understanding of the interrelationship between diet, intestinal microbiome and body immune system are fundamental in
the development of therapeutic approaches for various diseases to
benefit human health. In this review, we demonstrate the dynamic
changes of gut microbiota associated with human genotypes, age,
and dietary factors. Moreover, we highlight dietary effects on the
shifts of gut microbiota, and the mechanisms through which resulting in obesity and other related disorders such as type 2 diabetes
and several cardiovascular diseases. Finally, the association between
the regulation of gut microbiota and intestinal metabolism that
closely related to obesity were discussed, too.

The Dynamic Changes of Gut Microbiota are

Associated with Human Genotypes, Age, and Dietary
Factors

Host genotypes
Gut microbial composition of the kinship relationships resemble with each other more than unrelated individuals (Dicksved and
others 2008; Turnbaugh and others 2009c), suggesting that the genetic background may be an important factor in selecting and shaping the intestinal microbiota. A study of 645 mice with the use of
quantitative trait loci (QTL) detection approach (an analysis to test
whether specific taxa cosegregate as quantitative traits with linked
genomic markers) revealed that for 18 host QTL, the host genetic
variation is correlated with relative abundances of specific microbial taxa, including at least one taxon from each of the Bacteroidetes,
MS 20131271 Submitted 9/9/2013, Accepted 1/15/2014. Authors are with School Firmicutes, Proteobacteria, and Actinobacteria phyla (Benson and othof Chemical Engineering & Technology, Tianjin Univ., Tianjin, 300072, China. ers 2010). Another clinical study of familial Mediterranean fever
Direct inquiries to author Huang (E-mail: [email protected]).
(FMF) patients by mutations in the MEFV genewhich encodes
the pyrin, a regulatory protein of innate immunity demonstrated

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C 2014 Institute of Food Technologists

doi: 10.1111/1750-3841.12397
Further reproduction without permission is prohibited

R: Concise Reviews
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Diet effects in gut microbiome and obesity . . .

Figure 1The gut microbial composition presents dynamic changes correlated with host genotypes, age, and dietary factors and antibiotics treatment.
Changes in microbiota composition and related microbial products exert influences through complex mechanisms on host immune and metabolic
functions resulting in obesity and associated disorders.

significant shifts in bacterial community structure such as decreased

total numbers of bacteria, lower diversity, and major changes in
bacterial populations within the Bacteroidetes, Firmicutes, and Proteobacteria phyla (Khachatryan and others 2008).
These findings highlight that there is an interaction between the
host genetics and a specific profile of commensal microbiota in the
human gut, which will be critical for future studies to understand
the association between the composition of gut microbiota and
complex diseases.

Age
The gut microbiota in various age groups present different characteristics (Figure 1). To realize the significant features of each
group and the reasons for them will help to enhance pertinence
and actual effects of further studies.
Infancy is a critical period for intestinal colonization. The
newborn infant gastrointestinal tract is almost sterile and initial
acquisition of infant gut microbiota can be from vagina, feces,
and hospital. The early colonizers after delivery mainly are Bifidobacterium, Clostridium, Ruminococcus, Enterococcus, Enterobacter, and
Bacteroides (Favier and others 2002; Marques and others 2010).
During the first 2 y of life, the composition of the infant intestine is volatile and susceptible to many factors (OToole and
Claesson 2010) including delivery mode (Adlerberth and Wold
2009; Dominguez-Bello and others 2010), feeding method (Or-

rhage and Nord 1999), and environmental factors (such as health

care, nutrition, and antibiotics). Accompanied by the fluctuations
of bacterial populations, the complexity of the bacterial community evolved gradually toward an adult-like configuration (Palmer
and others 2007; EGGESB and others 2011; Yatsunenko and
others 2012).
In adulthood, the gut microbial composition is relatively stable
and dominated by Firmicutes and Bacteroidetes. Although it undergoes multiple perturbations of diets, antibiotics, and/or new
species invasion, the conventional microbiota can protect against
changes to a certain extent. But if the perturbations overload the
capacity of the microsystem can tolerate, shifts in gut microbiota
occur and may induce dysbacteriosis resulting in a range of diseases
(Lozupone and others 2012).
The human gut microbiota undergoes substantial changes
through the aging process as well as the functionality of the host
immune system, resulting in a frail situation and a greater susceptibility to infections. Several studies have observed age-related
changes in the gut microbiota composition. For example, The
dominant roles of Firmicutes and Bacteroidetes keep unchanged during different life stages but the ratio of Firmicutes to Bacteroidetes
evolvesto be respectively 0.4, 10.9, and 0.6 for infants, adults,
and elderly individuals (Mariat and others 2009).
In a study explored the gut microbiota composition of 145 elderly (mean age, 75 y) people and 85 health adults (mean age,

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Diet effects in gut microbiome and obesity . . .

35 y) from 4 European countries, higher prevalence of Enterobacteria were foundin all subjects independent of the location (Mueller
and others 2006). Another published study probed into the agerelated differences in the gut microbial composition among young
adults, elderly (mean age, 70 y), and centenarians (>100-y old)
observed highly similarity in that of the former 2 groups, whereas
that of the centenarians showed highly difference. In the centenarians, Eubacterium limosum and relatives representative of the long
life were more than 10-fold increased. Additionally, the proportion
of facultative anaerobes enriched. By contrast, a marked decrease
of Bifidobacteria, Faecalibacterium prauznitzii, and relative symbiotic
species with reported anti-inflammatory properties was observed
in centenarians (Biagi and others 2010). All these findings suggest
that the gut microbial composition of the elderly vary from those
in adults.
The innate alteration of human gut microbiota with ageing
may have relation to some symptoms of aging such as lower gastrointestinal function (S tsepetova and others 2011). Better understanding of the features presented by different age ranges will help
to find the relationship between gut microbiota and age-related
illness, and further clarify the pathogenesis.

Dietary effects on gut microbiota

Dietary regulation to the gut microbiota of early life.
The development of gut community in early life is important to
shape the intestinal microbiota and immune system of the host in
later life (Olszak and others 2012).
Feeding type is one of the most essential factors that affect
the neonate gut microbiotic composition. Breast-fed infants were
mainly colonized with bifidobacteria (up to 90% of flora). Human milk oligosaccharides (HMOs) are considered functioning as
growth factors for beneficial gut bacteria, as inhibitory receptors
binding to different pathogens, and may promote development
of the early immune system (Kunz and others 2000; Hemarajata and Versalovic 2012). In contrast, bottle-fed infants harbor
more diverse microbiota groups including Bacteroides, Clostridium, and Enterobacteriaceae (Martin and Walker 2008; Martn and
others 2009). The more reasonable nutrition designed formulas
nowadays, which contain prebiotics such as galactooligosaccharides (GOS) and fructooligosaccharides (FOS), have been proven
to increase the number of Bifidobacteria and Lactobacilli in the gut.
In contrast, antibiotics play a negative role in the composition of
the infant gut microbiota, resulting in decrease of obligate anaerobes (for example, Bifidobacteria and Bacteroides; Martin and Walker
2008; Reinhardt and others 2009). Reduced bacterial diversity
of the infants intestinal flora precedes asthma (Abrahamsson and
others 2013), allergic sensitization, allergic rhinitis, and peripheral
blood eosinophilia in the childhood (Bisgaard and others 2011).
However, the gut microbiota effect vary with antibiotics (Penders
and others 2006). Decreasing excessive use of antibiotics and increasing the use of pre- and probiotics is effective in preventing
several important infant diseases such as necrotizing enterocolitis,
atopic eczema as well as improving short and long-term health
(Wall and others 2009).
To sum up, dietary modulation to the infant microbiota influences the developing immune system and thus affect immunological response to some pathogens in later life.
Long-term dietary regulation derived from different
cultures. Dietary history is associated with geography, cultural
practices, lifestyle, and socioeconomic status. Significant differences have been found among the gut microbiota of the Russian,
American, Danish, and Chinese groups (Tyakht and others 2013).
R444 Journal of Food Science r Vol. 79, Nr. 4, 2014

Similarly, comparisons have also been made between Korean gut

microbial communities and those members from other countries
including the USA, China, and Japan. UniFrac analysis revealed
that fecal microbial community of each country member showed
slight difference from each other at phyla level, with American
had higher Firmicutes, Japanese had higher Actinobacteria, and Korean and Chinese enriched in Bacterodetes (Nam and others 2011).
Thereby, gut microbial composition is likely linked to long-term
dietary style.
The intestinal microbiomes of rural children in Burkina Faso
who consumed a plant-rich diet were compared with that of children from Italy who consumed a low-fiber diet (De Filippo and
others 2010) and significant differences of gut flora and opposite
trend between the 2 groups were gotten: the African children had
lower levels of Firmicutes than of Bacteroidetes whereas the European children who had high levels of Enterobacteriaceae (Shigella and
Escherichia). In specific, the dominant genera of bacteroides in the
microbiota of African children were the Prevotella and Xylanibacter,
whereas those of the European children were the genera Bacteroides
and Alistipes. Prevotella and Xylanibacter can ferment both xylan and
cellulose in the rural diet of the African children to liberate energy.
The Bacteroides plebeius coding genes of porphyranases and agarases
are significantly more frequent in the gut microbiome of Japanese
than that of the North American population, which is associated
with the seaweeds-rich diet habits of Japanese since seaweeds is
a major resource of the Bacteroides plebeius (Hehemann and others 2010). Significant differences in the phylogenetic composition
of fecal microbiota were noted between U.S. residents and those
from Malawians and Amerindians (Yatsunenko and others 2012).
At species level, the non-U.S. adults had a higher prevalence of
the Prevotella genus than the U.S. residents. The enzyme composition (EC) representation in fecal microbiomes was also compared
to see if the distinctive features are evident. The ECs participates
in the catabolism of glutamine, simple sugars, sugar substitutes,
and host glycans have higher proportional representation in adult
U.S. fecal microbiomes, reflecting their typical western diet. In
contrast, the EC involved in the degradation of starch was at high
level in the Malawian and Amerindian microbiomes, reflecting
their corn-dominant diet (Yatsunenko and others 2012) .
The metagenomes of gut microbiota community structures
from Russian cities resembled those of Western countries, which is
presumably associated with increased consumption of meat products and processed food (Tyakht and others 2013). However, the
gut microbiota in rural residents of Russia are distinctly enriched
in Firmicutes and Actinobacteria (both are underrepresented in urban
residents), which is presumably associated with high consumption
of starch-rich bread and natural products (Tyakht and others 2013).
These findings imply that the dietary habits formed over a long
period of time may play a key role in the composition of gut
microbiota over other variables such as ethnicity, sanitation, and
climate. But the genetic differences in individuals among different
countries cannot be neglected. More carefully controlled studies
should be carried out to probe into the relationship between longterm dietary patterns and gut microbiota even without genetic
factors and other environmental variables.
Short-term regulation by diet patterns and food
ingredients. Food ingredients such as polysaccharides, fat, protein, and vitamins consumed by the host can be absorbed and
utilized by gut microbiota. The microbial species in humans gut
can be more adept at degrading polysaccharides than the hosts
themselves, resulting in higher production of short-chain fatty
acids (SCFAs) such as acetate, propionate, and butyrate. Different

microbial species have their preferential targets, and diet

microbe interactions within the gut are now thought to play an important role in host health with links to suppression of pathogens,
impact on blood lipids, and a reduced risk of developing metabolic
disorders (Costabile and others 2008). The research about the dietrelated effects on the gut microbiota is of great significance for the
human health. For example, the vegetarian diet and the Western
diet are 2 distinctly different diet patterns, in which the former
is characterized by high fiber and low fat and the latter is the
other way around. Several studies have detected the difference
of the gut flora composition between the 2 diet patterns. The
gut microbiota of vegetarians is dominated by Clostridium coccoides,
Clostridium ramosum (Finegold and others 1983; Hayashi and others 2002) and in the absent of Faecalibacterium prausnitzii (Hayashi
and others 2002). The clusters of F. prausnitzii were found at high
levels in groups who mainly consume fish and meat (Mueller and
others 2006).
A more strict-designed recent study observed a vegan or vegetarian diet can significantly change the human gut microbiota
compared with the omnivorous controls carefully matched for
age and gender. Specifically, a distinct decrease in the counts of
Bacteroides spp., Bifidobacterium spp., Escherichia coli, and Enterobacteriaceae spp. was found in vegans and vegetarians (Zimmer and
others 2011), whereas the total bacteria cells were unchanged. A
shift in the fluctuant nonstarch polysaccharides and some other
nutrients from meal can rapidly alters the composition of the microbiota (Turnbaugh and others 2009b; Sonnenburg and others
2010; Faith and others 2011; Goodman and others 2011).
Whole grain cereal is rich in dietary fiber and resistant starch
(RS) with protection from chronic diseases. A recent in vitro study
explored the impact of 2 different sized oat flakes on the human
gut microbial ecosystem (Connolly and others 2010a). The larger
one produced significant increases in Bifidobacterium in the latter
stages of fermentation whereas numbers declined for the smaller
one. Additionally, the smaller one resulted in a significant increase
in the Bacteroidese Prevotella group. The differences may be due to
varying types and levels of dietary fiber present after digestion in
particular RS (Bifidobacterium are known to ferment this dietary
fiber; Connolly and others 2010a).
A study of 10 human subjects under a controlled setting detected marked changes in the microbiota along with a dietary shift
from high-fat, low-fiber to low-fat, high-fiber diets within 24 h
(Wu and others 2011). But the short time was not sufficient to
change the dominant enterotypes distinguished primarily by levels
of Bacteroides (associated with protein and animal fat) and Prevotella
(associated with carbohydrates). Thus, altering enterotypes may
require a long-term dietary intervention, more in line with the
study comparing children from Italy and Burkina-Faso (De Filippo and others 2010; Wu and others 2011). A recent study of 14
overweight men with precisely controlled diets revealed rapid and
marked changes in the colonic microbiota and demonstrated the
influence of dietary intake with consequences for health (Walker
and others 2010). In this study, the subjects were provided successively with a control diet, diets high in resistant starch (RS) or
nonstarch polysaccharides (NSPs), and a low carbohydrate weight
loss (WL) diet. Detected by qPCR, Firmicutes bacteria related to
Ruminococcus bromii (R-ruminococci) and Eubacterium rectale increased in most volunteers on the RS diet, and the Oscillibacter
group was enhanced by both the RS and WL diets. The E. rectale
decreased, along with Collinsella aerofaciens, on WL diet. However,
the starch digestibility estimated from chemical analysis of the diet
and of 24 h fecal samples were subject to interindividual varia-

tion, with >60% of RS remaining unfermented in 2 volunteers

on the RS diet, compared to <4% in the other 12 volunteers.
These results may be due to profound differences in the response
of the microbial community to dietary change, and in microbial
fermentation of dietary substrates in the colon between individuals
(Walker and others 2010).
It has been shown that diets high in RS and NSP can respectively
benefit insulin sensitivity and phytochemicals release through the
microbial fermentative activity in the colon (Gill and Rowland
2002; Robertson and others 2005). Besides, diets containing RS
and NSP offer potential benefits in prevention of colorectal cancer
through the delivery of fermentation acids, in particular butyrate,
to the distal colon (McIntyre and others 1993; Duncan and others 2007). Additionally, studies have found that WL diets have
considerable influence on the composition and metabolic outputs
of the gut bacterial community (Duncan and others 2007, 2008;
Brinkworth and others 2009) .
Probiotics. Probiotics are defined as live microorganisms
which, when administered in adequate amounts to allow colonization of the colon, confer a health benefit on the host (Sanders
2008), of which the most common groups are the genera Lactobacillus and Bifidobacterium (Parracho and others 2007). Introducing
probiotics to human and mice can lead to variations in expression
of microbiome-encoded enzymes associated to plant polysaccharide metabolism (McNulty and others 2011). Probiotics have been
shown to maintain the normal microbial community structure, inhibit the invasion of pathogens in the human gut by increasing the
amount of mucus secretion, improve the mucosal integrity, and
reduce the gut permeability (Spinler and others 2008; Saulnier
and others 2009; OShea and others 2012; Shen and others 2013).
The ability of Bifidobacteria to improve gut barrier function and
reduce the intestinal endotoxin levels has been demonstrated in
several studies (Griffiths and others 2004; Wang and others 2004;
Wang and others 2006). Furthermore, probiotics can act on the
gut immune system and affect the gut epithelia and immune cells
sensitivity to microbes in the gut lumen (Thomas and Versalovic
2010). The potential use of probiotics in lowering necrotizing
enterocolitis risks in preterm infants and preventing infections in
immunocompromised patients are also discussed in some studies
(Martin and Walker 2008; Guillemard and others 2010; Mikelsaar
and others 2010; Tatum and others 2010).
Moreover, probiotics may function as a supplementary tool to
ameliorate obesity and associated disorders (Shen and others 2013;
Sommer and Backhed 2013). A study on diet-induced obese
mice has confirmed the anti-obesity effect of Lactobacillus rhamnosus PL60, a human originated bacterium (Lee and others 2006).
Another germ-free mice study revealed that Lactobacillus paracasei could decrease fat storage along with a high level of Angptl4,
which is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes (Aronsson and others
2010).
As growth promoters, probiotics have been widely used in the
animal farming industry for nearly 50 y, and are experimentally
shown to stimulate fattening in poultry (Angelakis and Raoult
2010), livestock (Anadon and others 2006) and mice (Angelakis
and others 2012). It is difficult to deny the hypothesis that probiotics may have the same effect in humans by altering the intestinal flora. High level of intestinal lactobacilli can increase risks of
obesity and hyperglycemia in healthy adults (S tsepetova and others
2011), but the effects of the probiotics for body weight and obesity
are deemed to be strain specific. For example, Lactobacillus ingluviei, Lactobacillus acidophilus are associated with a weight-gain effect,
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Diet effects in gut microbiome and obesity . . .

whereas Lactobacillus casei/paracasei, Lactobacillus plantarum, and Lactobacillus gasseri showed antiobesity effect (Million and others 2011,
2012). In a rats study compared the effects of 4 Bifidobacteria strains
on the body weight (BW) gains acquired different results: 1 strain
increased BW, 1 strain reduced BW, and the rest 2 had no significant influences on BW (Yin and others 2010). Therefore, the
supplementation of probiotics should be detailed in specific strains
and carefully evaluated before they are regarded as safe for human
use.
Prebiotics. Prebiotics refers to nondigestible food ingredients
that selectively stimulate the growth of one or a limited number of
microbes in the gut with beneficial effects for host health (Pharmaceutiques 1995; Roberfroid 2007; Saulnier and others 2009;
Roberfroid and others 2010).
The prebiotic-rich foods, such as Jerusalem artichokes and
chicory, have been reported the ability to regulate gut microbiota
by elevating the number of Bifidobacteria and Lactobacilli (Kleessen
and others 2007; Ramnani and others 2010) . To improve their applicability, prebiotics may serve as oral intake ingredients. Supplementation with prebiotics such as fructo-oligosaccharides (FOS)
and inulin can promote the growth of beneficial gut bacteria, particularly Bifidobacterium and/or Lactobacillus (Ramirez-Farias and
others 2009; Brignardello and others 2010; Maccarrone and others 2010; Roberfroid and others 2010; Cani and others 2012),
and decrease the number of Clostridium leptum in some studies
(Pyra and others 2012). Interestingly, some fructans are also able
to increase other bacteria such as F. prausnitzii (Ramirez-Farias and
others 2009).
Several mechanisms (Table 1) have been proposed to illustrate
the beneficial effects of prebiotic on obesity and related metabolic
disease such as type 2 diabetes and several cardiovascular disease :
(1) a modulation of gut peptides (glucagon-like peptide 1, peptide YY, and intestinal proglucagon mRNA) with consequences
for a decrease in appetite and postprandial glucose excursion responses (Cani and others 2009a; Parnell and Reimer 2009; Everard
and others 2011; Hess and others 2011). (2) Increasing endogenous glucagon-like peptide-2 (GLP-2) production resulting in the
amelioration of gut barrier functions during obesity and diabetes
(Cani and others 2009b). (3) Improving glucose tolerance, target
enteroendocrine cell activity, and leptin sensitivity associated with
metabolism in obesity and diabetes (Cani and others 2009b; Everard and others 2011). (4) Promoting gut fermentation and modulating GPR43 (a G protein-coupled receptor, linking between
gut fermentation processes and white adipose tissue development)
expression, thus controlling the development of adipose tissue
(Dewulf and others 2011). (5) Regulating inflammatory tone by
a decrease in endotoxaemia, plasma, and adipose tissue proinflammatory cytokines, as well as hepatic expression of inflammatory
and oxidative stress markers, which may affect host metabolism in
obesity and diabetes (Cani and others 2007, 2009b).
Antibiotics. Antibiotics are designed to target pathogenic
population and improve our lives by treating infectious diseases.
But because most of them have broad-spectrum activity, they can
affect other members of the gut microbiota and thereby disrupt
their coevolved interactions with the host.
The alterations in the gut microbiota as a result of antibiotic
treatment mainly come down to a shift in microbiota composition (Dethlefsen and others 2008; Dethlefsen and Relman 2011),
reduced diversity, and/or abundance of bacteroides (Dethlefsen
and others 2008; MacFarlane and Macfarlane 2009; Dethlefsen
and Relman 2011), and decreased evenness of the community
(Dethlefsen and others 2008). But community changes induced
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by antibiotic treatment varied among individuals, which may be

due to the expansion of antibiotic-resistant genes in the gut microenvironment and other indirect factors (Dethlefsen and others
2008).
Disrupted interactions within the gut flora resulting from antibiotic usage are reported in associated with acute (Beaugerie and
Petit 2004) and chronic (Floistrup and others 2006; Marra and
others 2006) health problems, such as obesity (Ternak 2005), diarrhea, asthma, and IBD (Guarner and others 2006). Significant
and persistent weight gain can occur after treatment with a 6-wk
intravenous treatment of vancomycin in patients with infective
endocarditis, which might be due to the selection of Lactobacillus
sp. in the gut microbiota (Thuny and others 2010). Antibiotic
therapy can also prevent from obesity as well as improve plasma
lipopolysacharides (LPS) levels and glucose tolerance (Kalliomaki
and others 2008; Membrez and others 2008).
A study of the infant gut flora following ampicillin and gentamicin treatment indicated that the gut microbiota of the antibiotictreated infants significantly changed (with a higher proportions of
Proteobacteria and lower proportions of Actinobacteria as well as the
genus Lactobacillus than the untreated counterparts) and recovery
still incomplete after 8 wk, which suggests antibiotics disruption
in early life can exert crucial influences on the evolution of the
infant gut microbiota (Fouhy and others 2012).
Although the composition of human gut microbiota changes
naturally with age, the impact of antibiotic therapy on the elderly
intestinal microbiota composition taking into account their residence location (long-term nursing care, rehabilitation wards, day
hospitals, and the community) was recently discussed (OSullivan
and others 2013). The study revealed that a significant structural
shift across 9 genera in the antibiotic-treated subjects, including a
7-fold reduction in Bifidobacterium spp. numbers. Thus, the longterm health effects following antibiotic therapy on the intestinal
microbiota in the elderly should be considered (OSullivan and
others 2013).
The mechanisms of the microbiota modulation toward host
metabolic and immune system induced by antibiotic treatment are
complex and largely unclear. The known hypothesizes at present
may include (1) Effects on microbial intestinal metabolism: gut
bacteria respond to antibiotic usage attenuated the production of
SCFAswhich is the main energy source and associated with
cell proliferation, differentiation, growth, and apoptosis (Willing
and others 2011)and the capacity to transport and metabolize
bile acid, cholesterol, hormones, and vitamins (Perez-Cobas and
others 2013). (2) Perturbation in intestinal homeostasis and the
integrity of intestinal defenses: a study with metronidazole-treated
mice indicated that disruption of the microbiota with antibiotic
resulted in an increased inflammatory tone of the gut, which is
characterized by increased bacterial (C. rodentium) stimulation of
the epithelium, altered goblet cell function, and reduction in mucus thickness. It demonstrates a impaired mucosal barrier and thus
contributes to the exacerbated severity of C. rodentium-induced
colitis (Wlodarska and others 2011). (3) Distribution to the innate
immunity: lower diversity of the microbiota following antibiotic
treatment can decrease the amount of microorganism-associated
molecular pattern (MAMP) recognition receptors, for example
Toll-like receptors (TLRs), which are activated by bacterial ligands and thereby weakening the innate immunity (Dessein and
others 2009; Wells and others 2010). (4) Regulation of T-cell differentiation and activation: depleting Gram-positive bacteria especially segmented filamentous bacteria population with antibiotics
reduces the differentiation of T-helper 17 cells, thus resulting in a

Male C57bl6/J mice: fed a

standard diet or an HF diet
without or with Inulin-type
fructans (ITF) (0.2 g/d per
mouse) during 4 wk
Male lean and obese JCR:LA-cp
rats: received different dose of
inulin and oligofructose
20 healthy subjects: assigned to
receive 2 separate doses of 0, 5,
or 8 g of short-chain
fructooligosaccharide (scFOS)
48 healthy adults with a body
mass index (in kg/m2 ) > 25
consumed 21 g oligofructose/d
or a placebo (maltodextrin) for
12 wk
Male, diet-induced obese
SpragueDawley rats: fed with
high-fat/-sucrose diet plus
either metformin (MET) or
oligofructose (OFS) or both

10 healthy adults (5 men and 5

women) were randomly
divided into 2 groups: received
either 16 g prebiotics/d or 16 g
dextrin maltose/d for 2 wk
1. ob/ob mice (Ob-CT):
prebiotic treatment (Ob-Pre) vs
control (Ob-Cell)
2. Ob-CT and Ob-Pre mice were
treated with GLP-2 antagonist
or saline
3. Ob-CT mice were treated with
a GLP-2 agonist or saline
ob/ob mice or diet-induced obese
and diabetic mice: chronically
fed with prebiotic-enriched
diet or with a control diet

HF-feeding mice vs normal

chow-fed control mice and
HF-OFS-treated mice

Animal model and

experimental design

Bifidobacteria Clostridium leptum

Firmicutes Bacteroidetes Bifidobacteria

and Lactobacillus(in a
dose-dependent manner)

Fat mass, hepatic total glycerin,

glucose-dependent insulinotropic
polypeptide (GIP) secretion, leptin,
AMPK2 mRNA and phosphorylated
acetyl CoA carboxylase (pACC) levels,
plasma DPP4 activity

The potential to improve metabolic

outcomes associated with obesity

The potential to promote weight loss and

ameliorate satiety hormone
concentrations and glucose regulation in
overweight adults

Plasma ghrelin response and peptide YY

A beneficial effect on obesity and with

potential decrease in PPAR- activated
processes

Exerting effects on host metabolism in

obesity and diabetes

Vol. 79, Nr. 4, 2014 r Journal of Food Science R447

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Pyra and others 2012

Parnell, and Reimer 2009

Hess and others 2011

Parnell and Reimer 2012

Dewulf and others 2011

Everard and others 2011

Cani and others 2009

Improving inflammation and metabolic

disorders during obesity and diabetes;
improve gut barrier functions

Dose-dependent regulation of the appetite

effects and energy expenditure may have
therapeutic potential for obesity
The potential of scFOS as a dietary
intervention is still remained to be seen

Glucose tolerance, L-cell

number(intestinal proglucagon mRNA
expression and plasma glucagon-like
peptide-1 levels), fat-mass development,
fat oxidative stress, and low-grade
inflammation, leptin sensitivity
Peroxisome proliferator activated receptor
(PPAR- )activated differentiation
factors, GPR43 expression, the
subcutaneous adipose tissue

Firmicutes Bacteroidetes

Cani and others 2009

Cani and others 2007

Reference

Changes in appetite sensation and glucose

excursion responses after a meal

Improving high-fat-diet-induced diabetes

in mice

Functions on disease

Caecal proglucagon and peptide YY mRNA

levels, plasma ghrelin response (in a
dose-dependent manner)
Gastrointestinal tolerance , breath
hydrogen(in a dose-dependent manner ),
the appetite effects was not obvious

Inflammatory tone (plasma LPS and

cytokines, hepatic expression of
inflammatory and oxidative stress
markers); the endogenous
intestinotrophic proglucagon-derived
peptide (GLP-2) production, intestinal
permeability

Bifidobacterium spp.

Bifidobacterium spp. Roseburia spp.

C. coccoides

Glucose tolerance, glucose-induced insulin

secretion;normalized inflammatory tone
endotoxaemia, plasma and adipose tissue
proinflammatory cytokines
Plasma glucagon-like peptide 1 and peptide
YY concentrations

Mechanism

Bifidobacterium spp.

Flora change with prebiotics

Table 1Studies of the mechanisms and beneficial effects of prebiotics on obesity and related metabolic disease.

Diet effects in gut microbiome and obesity . . .

R: Concise Reviews
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Diet effects in gut microbiome and obesity . . .

depletion of the secretion of related pro-inflammatory cytokines Gpr41+/+ and Gpr41/ mice revealed that the former group
are significantly fatter than the latter counterparts no matter they
(Ivanov and others 2009).
were normally raised or gnotobiotic. And it indicated that the
Gut Microbiota and Obesity
knockout of Gpr41 is corresponding with decreased expression
Obesity, now considered a worldwide epidemic, is a major of PYY, an intestinal secreted hormone negatively regulating gut
health problem in both developed and developing countries (Eckel motility, satiety, and energy expenditure (Samuel and others 2008).
and others 2004). It has many complications such as type 2 diabetes A study with Gpr43-deficient mice fed a high-fat diet has shown
mellitus, hypertension, obstructive sleep apnea syndrome, and is- lower body fat mass in them as well as lower levels of liver triglycchemic heart disease (Steelman and others 2002). More recently, erides and plasma cholesterol, suggesting the inhibiting effect of
obesity is even recognized as a risk factor for cancer (Khandekar Gpr43 in energy expenditure and triglyceride synthesis (Bjursell
and others 2011; Yoshimoto and others 2013). The causes behind and others 2011).
obesity appear to be multiple and involve genetic background,
disequilibrium in the energy balance, living a sedentary lifestyle, Expression of obesity-related genes in the host
and other environmental factors (Friedman 2009). For the past
Angiopoietin-like protein 4 (Angptl4), also called fastingfew years, obesity has been associated with a modification in mi- induced adipose factor (Fiaf), is a circulating lipoprotein lipase
crobiota, including a higher Firmicutes/Bacteroidetes ratio (Ley and inhibitor expressed in the intestine and selectively inhibited in
others 2006a) and a decrease in Methanobrevibacter smithii (Turn- the gut epithelium by the microbiota resulting in accumulation of
baugh and others 2006). Additionally, it has been shown that the adipocyte triglycerides (Backhed and others 2004, 2007). Corregut microbiota of nonobese individuals is more diverse than that of spondingly, the overexpression of Angptl4 reduces adipose tissue
obese individuals (Turnbaugh and others 2009a). The mechanisms weight by stimulating triglyceride metabolism (Mandard and othby which gut microbiota affect obesity in humans are complicated ers 2006). Moreover, downregulated expression of AMP-activated
and largely unknown, the proposed statements may consist of: an protein kinase (AMPK) by gut microbiota induces inhibition
excessive bodily energy harvest, higher levels of SCFAs to promote of fatty-acid oxidation resulting in obesity (Backhed and others
adipogenesis, overexpression of the obesity-related genes, and in- 2007).
creased production of LPS by gut microbiota causing obesity and
Inflammation (Figure 1).
High levels of LPS induced by gut microbiota
In both studies of humans and mice, positive correlations have
An excessive energy intake of the host
been found between energy intakes and plasma LPS levels (Cani
Several obese mice and humans studies have observed signifi- and others 2007; Amar and others 2008). LPS is a compound
cant shifts in the intestinal phyla usually with an increase in Firmi- from Gram-negative bacterial cell walls whose concentration is up
cutes/Actinobacterium and a reduction in Bacteroidetes (Waldram and along with an increase in the proportion of Gram-negative bacothers 2009; Ley 2010; McNulty and others 2011). These mi- teria induced by a fat-rich diet (Cani and others 2007; Amar and
crobiota changes resulted in an increased capacity for the fermen- others 2008). Excessive high level of LPS (defined as metabolic
tation of carbohydrates (Turnbaugh and others 2006; Turnbaugh endotoxemia) is related to gut, hepatic, and adipose tissue inflamand others 2009c) and further an increased concentration of the mation and diabetes through complex mechanisms (Cani and othend productSCFAs, mainly acetate, propionate, and butyrate ers 2007; Amar and others 2008; Seki and Brenner 2008; Fei and
which are crucial energy substrates of the host (Turnbaugh and Zhao 2013). Another possible mechanism proposed is that highGordon 2009). However, some studies failed to disclose the re- fat feeding triggers alterations in intestinal microbiota, followed by
lationship between the dominant gut phyla and obesity (Duncan a decrease in IAP activity and an increase in TLR4 activation in
and others 2008; Connolly and others 2010b). These contradic- the gut wall, then leading to an increase in luminal LPS and gut
tory results probably due to the individual variations and effects permeability (de La Serre and others 2010). Enhanced gut perof multiple environmental factors inevitably. In another example, meability could increase plasma levels of LPS, finally resulting in
Bacteroides thetaiotaomicron along with M. smithii are colonized in an appearance of hyperphagia and obesity (de La Serre and others
germ-free mice. Since M. smithii uses the production of B. thetaio- 2010). Germfree mice colonized with Enterobacter cloacae B29 (an
taomicron (formate) as substrate for methanogenesis, on the one endotoxin-producing bacterium) isolated from a morbidly corpuhand the degradation of carbohydrate is enhanced thus improving lent humans gut induced obesity and insulin resistance characbodily energy gain (Samuel and Gordon 2006); however, a higher terized by high levels of circulating endotoxin and deteriorative
concentration of methane is associated with a higher body mass inflammatory status (Fei and Zhao 2013). Meanwhile, the sympindex and is a predictor of significantly overweight (Basseri and toms are more apparent on a high-fat diet than a normal chow
others 2012).
diet. It is a commendable interpretation of the diet-microbiotaLPS-obesity association (Fei and Zhao 2013).

Regulation in SCFAs to activate adipose tissue

development
Apart from being an important energy sources, the SCFAs
are ligands for specific G-proteincoupled receptors (GPCRs)
Gpr41 (expressed by a subset of enteroendocrine cells in the gut
epithelium) and Gpr43 (is activated by SCFAs and expressed in
intestine, adipocytes, and immune cells, suggesting involvement
in lipid and immune regulation; Brown and others 2003; Le
Poul and others 2003)which may promote energy absorption
and/or triglyceride synthesis and may further affect immune and
inflammatory responses (Maslowski and others 2009). Studies on
R448 Journal of Food Science r Vol. 79, Nr. 4, 2014

Conclusions and Prospects

In this review, we have summarized the crucial roles of genetic,
physiological, and dietary factors in gut microbiota composition,
and further discussed the interactions between gut microbiota and
obesity. But the interrelationship between the microbiota, the environment, and human health is a profound and complex problem,
especially the exact mechanisms through which microbes regulate the host metabolism. A metabolomics study has shown the
pathway linking dietary lipid intake, intestinal microbiome, and
atherosclerosis, which provides opportunities for the development

of novel therapeutical approaches for atherosclerotic heart disease

(Wang and others 2011). Deeper analysis into microbial metagenomics, metatranscriptomics, and metabonomics to get a better
understanding of the specific functional genes and their mechanisms for health is of great significance. Besides, more research is
needed to understand how the inter-individual variation is modified by age and genetic environmental factors and how to make
a distinction between bacterial groups those are beneficial and
those are detrimental to health. Advanced culture-independent
approaches and bioinformatics tools facilitate the large-scale sequencing of human gut microbiome. However, most of data acquired to date have been from fecal samples while ignoring the
microbial metabolism occurring in small intestinal. Thus, using
these meta-omicsbased methods to track the changes of microbial metabolism in different gut site over time is a major challenge.
Experimental animal models, particularly the humanized
germ-free mice and/or genetically modified mice, help to identify
the correlations between dietary components and gut microbial
communities as well as the relevant mechanisms impacting host
metabolism. To confirm the effects of gut microbiota on human
metabolic disorders and long-term state of health, well-controlled
clinical-level studies must be carried out.
As probiotics and/or prebiotics are increasingly used in industrial food such as fermented milk products contain Bifidobacterium,
Lactobacillus, and/or xylooligosaccharide, the application of both
in modulating gut microbiota composition is a potential therapeutic use. However, attentions should be paid to the exploration
of new-type prebiotics and the safety of probiotics, as well as the
unpleasant side effects from both. For example, in vitro studies
have investigated the prebiotic potential of a konjac glucomannan hydrolysate (GMH), polydextrose, and several polyols using
batch culture fermentations (Beards and others 2010; Connolly
and others 2010b). Probiotics effects on body weight and obesity
are recognized to be strain specific and dose dependent, thus it
is essential to enforce stringent level of control before they are
regarded as safe for human use. Synbiotics, in which probiotics
and prebiotics are used in combination, are normally used to regulate the composition of the gut microbiota contributing to health
care or disease prevention (Vitali and others 2010). As the exact
molecular mechanisms underlying their health benefits have remained largely unclear, carefully designed clinical trials should be
performed in urgently needed.
In conclusion, manipulation of the gut microbiota by integrated
factors significantly affects the host metabolism. Discoveries in this
area provide us novel perceptions to the micrbiotahost interactions and will promote the development of therapeutic approaches
for obesity and its complications.

Acknowledgments
This work was supported by the National Natural Science
Foundation of China (Nr. 31272540) and the National high technology research and development program of China (863 program,
Nr. 2012AA101605).

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