A Microbiota Intestinal Humana - Metabolismo e Perspectiva Na Obesidade
A Microbiota Intestinal Humana - Metabolismo e Perspectiva Na Obesidade
A Microbiota Intestinal Humana - Metabolismo e Perspectiva Na Obesidade
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To cite this article: Aline Corado Gomes, Christian Hoffmann & João Felipe Mota (2018):
The human gut microbiota: metabolism and perspective in obesity, Gut Microbes, DOI:
10.1080/19490976.2018.1465157
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DOI: https://doi.org/10.1080/19490976.2018.1465157
1
Clinical and Sports Nutrition Research Laboratory (LABINCE), Faculty of Nutrition, Goiás Federal
2
Department of Food Sciences and Experimental Nutrition, School of Pharmaceutical Sciences,
*Corresponding author:
Dra. Aline Corado Gomes, Clinical and Sports Nutrition Research Laboratory (LABINCE), Faculty of
St. 227, Block 68, Setor Leste Universitário. Goiânia GO, Brazil, 74.605-080.
Abstract
The gut microbiota has been recognized as an important factor in the development of metabolic
diseases such as obesity and is considered an endocrine organ involved in the maintenance of energy
homeostasis and host immunity. Dysbiosis can change the functioning of the intestinal barrier and the
gut-associated lymphoid tissues (GALT) by allowing the passage of structural components of
bacteria, such as lipopolysaccharides (LPS), which activate inflammatory pathways that may
contribute to the development of insulin resistance. Furthermore, intestinal dysbiosis can alter the
obese people, this dysbiosis seems be related to increases of the phylum Firmicutes, the genus
Clostridium, and the species Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri,
Introduction
The gut microbiota has recently been recognized as an important factor for the development
of metabolic diseases and is considered an endocrine organ involved in the maintenance of energy
homeostasis and host immunity [1]. Changes in the composition of the gut microbiota due to
environmental factors may result in a change in the relationship between the bacteria and the host.
This change can result in a low-grade chronic inflammatory process and in metabolic disorders such
The human gut microbiota consists of up to 100 trillion microbes that exist in a largely
symbiotic relationship with their human hosts, carrying at least 150 times more genes (the
microbiome) than the human genome [3]. Based on 16S rRNA-targeted molecular analyses, most
bacteria detected in fecal samples from healthy human volunteers belong to two phyla, Bacteroidetes
and Firmicutes. The gram-negative Bacteroidetes phylum includes the genera Bacteroides, Prevotella,
Parabacteroides, and Alistipes, while the gram-positive Firmicutes includes species such as
Faecalibacterium prausnitzii, Eubacterium rectale, and Eubacterium hallii [4], as well as many other
The metabolism of some bacteria can facilitate the extraction of calories from the diet,
increase fat deposition in adipose tissue, exacerbate hepatic inflammatory processes, and provide
energy and nutrients for microbial growth and proliferation [5,6]. Several microbial genes involved in
human metabolism are enriched or depleted in the guts of obese humans [7]. Obese people tend to
have a higher proportion of genes which encode membrane transport functions [8] and are involved in
butyrate production, [9] whereas the genes related to cofactor, vitamin, and nucleotide metabolism or
Considering this influence of the gut microbiome on the onset and progression of obesity as
well as its consequences, knowledge about the gut microbiota could contribute to the development of
adjuvant treatments that can beneficially modulate obesity. Some studies have already evaluated the
gut microbiota composition in obese individuals; however, the characterization of this microbiota is
still not well established, and some results are discordant. Here, we present a review of the
physiology and composition of the human gut microbiota with a focus on obese individuals. We
divided our review into two topics: the physiology of the gut microbiota and the composition of this
Methods
systematized literature search that included observational studies (cross-sectional, cohort, or case-
control) and experimental studies. The following exclusion criteria were used to reduce possible
relationships observed due to other comorbidities: diabetes, intestinal diseases, cancer, experimental
studies, and studies that supplemented gut microbiota modulators. The literature search was
performed in the MEDLINE and Scopus databases, and the references of studies obtained were
scanned for other relevant articles that may not have been detected by the primary search. Only
studies published in English in the last 10 years were considered for review. The following Medical
Subject Headings (MeSH) search strategy was used: ((obesity[Title/Abstract] AND full text[sb] AND
"last 10 years"[PDat]) AND (gut microbiota composition[Title/Abstract]) AND (full text[sb] AND
conference case-control studies, cohort studies, and cross-sectional studies, and CONSORT
reporting trials of nonpharmacological treatments. The final system was a combination of STROBE
and CONSORT.
We also conducted a narrative review about the subject in the following topics: function of the
gut microbiota on the development of lymphoid structures, function of the gut microbiota on the
immune system, function of the gut microbiota on nutrient and lipid metabolism, function of the gut
microbiota on the hormones involved in food intake, and gut microbiota and obesity: future
perspectives. There were no restrictions placed on the year of publication in this section.
The gut microbiota harbors incredibly large microbial and genetic diversity, with distinct
species associated with specific parts of the gastrointestinal tract. The stomach contains about 101
microbial cells per gram of content. The duodenum contains about 103 cells; the jejunum ,104 cells; the
ileum, 107 cells; and the colon, 1012 microbial cells per gram of contents [10]. Therefore, the quantity
of bacteria increases from the proximal to the distal portions of the gastrointestinal tract. Notably, the
large intestine contains more than 70% of all microorganisms in the body, which are usually
associated with the health/disease of the host [11]. In addition, the diversity of bacteria is higher in the
High numbers of bacteria in the gastrointestinal tract result in biochemical diversity and
metabolic activity that interacts with host physiology. These microorganisms can facilitate the
metabolism of non-digestible polysaccharides, produce essential vitamins, and they also play an
important role in the development and differentiation of the intestinal epithelium and the host immune
system [13].
Most species are anaerobic and belong to two phyla: Firmicutes and Bacteroidetes. Bacteria
Cyanobacteria are widely spread in human populations, but at much lesser abundance [14]. Although
controversial, the ratio of Firmicutes-to-Bacteroidetes has been investigated and associated with the
predisposition of diseases [15]. Moreover, the low abundance of phylum Proteobacteria associated
with a high amount of the genera Bacteroides, Prevotella, and Ruminococcus has been associated
with a healthy intestinal microbiota [16]. The maintenance of a healthy gut microbiota is important for
The lymphatic system consists of a set of lymphatic vessels that interconnect primary to
secondary lymphoid organs. Recirculation of the interstitial fluid and the transport of lymphocytes
and antigen-presenting cells occur through this system. These immune cells are produced in the
primary lymphoid tissues (thymus and bone marrow) and are activated in the secondary lymphoid
tissues (spleen, lymph nodes, and mucosa-associated lymphoid tissue (MALT)). [17]
Among the MALT, the gut-associated lymphoid tissues (GALT) are non-encapsulated tissues
composed of Peyer's patches, isolated lymphoid follicles, and crypt plaques [18] that begin to form
during embryogenesis, when the environment is sterile. At this stage, the mesenchymal cells are
induced by retinoic acid to produce the chemokine (C-X-C motif) ligand 13 (CXCL13) that attracts
the human lymphoid tissue inducer (LTi) cells. Mature LTi cells induce differentiation of stromal
cells and attract immune cells, which form the GALT [17].
The maturation of this tissue depends on microbial colonization after birth [19]. The stromal
and epithelial cells recognize bacterial peptidoglycan through the signaling pattern recognition
like receptors (TLRs). Activation of these receptors by the gut microbiota increases the expression of
CC chemokine ligand 20 (CCL20) and β defensin 3 ligand (HBD3), which activate the formation of
isolated lymphoid follicles from the binding of chemokine receptor 6 (CCR6) in LTi [20]. Changes in
the microbial composition, which happens in obese individuals, can further disrupt the integrity of the
intestinal barrier promoted by GALT, leading to pathological bacterial translocation and the initiation
Besides acting on the maturation of GALT, the commensal bacteria also prevent the intestinal
colonization by pathogens. The gut microbiota improves the function of the epithelial barrier, while
its absence decreases the production of antimicrobial peptides by Paneth cells. This event causes
intestinal barrier dysfunction and increases bacterial translocation [22]. Furthermore, bacteria-induced
myeloid differentiation factor 88 (MyD88) signaling in the intestine increases epithelial cell IgA
secretion. In addition, bacterial flagellin activates Toll-like receptors 5 (TLR5) from dendritic cells,
and promotes the differentiation of B lymphocytes into IgA-producing cells [23.] IgA binds to the
microbial antigens, neutralizes the activity of the pathogens, and prevents infection [24].
Commensal bacteria modulate the innate immune response of the host by stimulating the
production of homeostatic levels of pro-IL-1β by resident macrophages so that the response of these
cells to an enteric infection occurs more rapidly [25]. The protective role of IL-1β in intestinal
Besides that, modulation of natural killer (NK) T cells is also performed by commensal
bacteria. NK T cells are a subset of T cells that simultaneously express both T cell receptor (TCR) and
NK cell receptors. These cells promote inflammation from the secretion of cytokines IL-2, IL-4, IL-
13, IL-17A, IL-21, tumor necrosis factor (TNF), and interferon-γ (IFN- γ) [27]. Maintenance of
diseases, such as cardiovascular disease [29] and type 2 diabetes [30]. Intestinal dysbiosis (changes in
gut microbiota composition) can be related to the trigger of a persistent low-grade inflammatory
response in obese individuals. Lipopolysaccharides (LPS) contain lipid A, which can cross the
intestinal mucosa through tight junctions or with the aid of chylomicrons [31,32]. Lipoproteins are
responsible for the absorption and transport of dietary triglycerides, and could thus initiate an
inflammatory process that could result in the insulin resistance often observed in obesity [31,32]. In
the systemic circulation, LPS causes an innate immune response in liver and adipose tissue. This
occurs from the binding of LPS to the LPS binding protein (LBP), which activates the CD14 receptor
[32]. This complex binds to Toll-like 4 receptors (TLR4) on macrophages and adipose tissue,
resulting in a signaling pathway that activates the expression of genes encoding pro-inflammatory
proteins, such as factor nuclear kappa B (NF-κB) and activator protein 1 (AP-1) [32,33].
LPS concentrations are low in healthy people, but may reach high concentrations in obese
individuals and cause metabolic endotoxemia [31]. This metabolic endotoxemia is related to the
development of insulin resistance [34]. The molecular mechanisms that relate the activation of TLR4
by LPS with insulin resistance still need to be clarified, but evidence indicates that it involves
The gut microbiota derives its nutrients from the fermentation of carbohydrates ingested by
the host. Bacteroides, Roseburia, Bifidobacterium, Fecalibacterium, and Enterobacteria are among
the bacterial groups that typically ferment undigested carbohydrates and synthesize short chain fatty
acids (SCFA) [36] such as acetate, butyrate, and propionate. A significant amount of acetate enters the
systemic circulation and reaches the peripheral tissues, while the propionate is mainly used in liver,
and the butyrate is used in intestinal epithelium as an energy source [37]. The total and relative
concentrations of SCFA depend on the fermentation site, the carbohydrate consumed, and the
the Firmicutes and Actinobacteria phyla are conjugated linoleic acid (CLA) producers [39]. CLA is a
mixture of positional and geometric isomers of linoleic acid shown by some studies to have anti-
obesity properties such as: increase in energy metabolism and expenditure, decrease in adipogenesis,
decrease in lipogenesis, and increase in lipolysis and adipocyte apoptosis [39]. The biological effects
of CLA have been attributed to two possible mechanisms of action: 1) CLA displaces the arachidonic
acid from cell membrane phospholipids, which decreases the synthesis of arachidonic acid-derived
eicosanoids such as prostaglandins and leukotrienes involved in inflammation [40], and 2) CLA
(PPARs), which impact cell processes such as lipid metabolism, apoptosis, and immune function [40].
The gut microbiota of obese mice had a higher amount of genes that encode enzymes
involved in carbohydrate metabolism and greater capacity to extract energy from the diet and to
produce SCFA when compared to non-obese mice [41]. In addition, germ-free mice were resistant to
SCFAs bind to G protein-coupled receptors (GPCR41 and GPCR43) [36]. Acetate binds
primarily to GPCR43, the propionate binds to both GPCR41 and GPCR43, and the butyrate binds to
GPCR41. GPCR41 and GPCR43 receptors are expressed in the intestinal epithelium [37] and in
adipose tissue [36]. The presence of GPCRs in adipose tissue suggests that this tissue is an important
target for the metabolites produced by the gut microbiota. One study identified that rats fed a high fat
diet had higher GPCR43 expression in adipose tissue and in vitro. SCFA increased the expression of
PPARs, an important mediator of adipogenesis [43]. SCFAs that are bound to GPCR41 stimulate the
expression of leptin in adipocytes and those that bind to GPCR43 appear to stimulate adipogenesis
[44]. Thus, the profile of fatty acids produced may be related to the development of obesity. However,
Lipid metabolism
The endocannabinoid system is expressed in tissues that control energy balance (pancreas,
muscle, gut, fat, liver, and hypothalamus) and regulates feeding behavior and metabolism [45]. This
system is composed of bioactive lipids that bind to cannabinoid receptors, which results in cell
signaling. The best characterized of these lipids are anandamide (AEA) and 2-arachidonoylglycerol
(2-AG) [46], which activate receptors coupled to G, CB1, and CB2 proteins, thus activating the
PPARα, GPR55, and GPR119 receptors [47]. The modulation of the gut microbiota or the reduction
of CB1 activation improves the integrity of the intestinal barrier and reduces metabolic endotoxemia
and low-grade inflammation [47]. Metabolic endotoxemia increased adipocyte hyperplasia and
recruitment of macrophages into adipose tissue in a CD14 dependent pathway and increases the
production of activin A, which activated the proliferation of adipocyte precursor cells. In addition, the
consumption of a high fat diet caused endotoxemia and favored the development of metabolic
diseases, suggesting that components of gut bacteria can remodel adipose tissue [48]. The control of
this mechanism can prevent the development of obesity and its comorbidities [48].
In addition to altering the adiposity process, the microbiota acts at many levels, from lipid
processing and absorption to systemic lipid metabolism [49,50]. This change can be explained by the
assimilation of cholesterol by bacterial cells, binding of cholesterol to bacterial cell walls, inhibition
of hepatic cholesterol synthesis, redistribution of cholesterol from the plasma to the liver through the
Evidence also suggests a link between dysbiosis and pathological changes in the
metabolism of deconjugated bile acids in obese patients [52]. Bacterial bile salt hydrolase (BSH)
enzymes in the gut cleave the amino acid side chain of glyco- or tauro-conjugated bile acids to
generate unconjugated bile acids (cholic and chenodeoxycholic acids), which are then amenable to
further bacterial modification to yield secondary bile acids (deoxycholic and lithocholic acid) [53].
Secondary bile acids binded to cellular receptors, such as G protein-coupled receptor TGR5 [54], and
reduced macrophage inflammation and lipoprotein uptake resulting in less atherosclerotic plaque
The gut microbiota has been implicated in the control of food intake and satiety through gut
peptide signaling, where bacterial products activate enteroendocrine cells by modulating enterocyte-
produced paracrine signaling molecules [56]. Gut microbiota may increase production of certain
SCFA, which have been shown to be associated with an increase in peptide YY (PYY) [57], ghrelin,
coccoides/Eubacterium rectale, and positively correlated with Bacteroides and Prevotella [59].
Ingestion of oligofructose, a prebiotic that promotes the growth of Bifidobacterium and Lactobacillus,
GLP-1 also is modulated by the gut microbiota and is responsible for controlling food intake
and insulin secretion. The concentration of this hormone was lower in obese individuals compared to
eutrophic individuals [61,62]. Butyrate produced by intestinal bacteria was present in smaller amounts
in obese individuals [63] and regulated energetic homeostasis by stimulating adipocytes to produce
leptin and by inducing GLP-1 secretion by L cells [64]. At least in mice, modulation of the gut
microbiota by probiotics increased the production of butyrate by commensal bacteria, inducing the
In addition, the gut microbiota may favor the formation of specific bile acids that activate the
TGR5 receptors. Intestinal bacteria dehydrate chenodeoxycholic acid [66] and produce lithocholic
acid, which binds to TGR5 [67] and increases energy expenditure in brown adipose tissue and GLP-1
secretion by activation in the intestinal L cells [54], thus preventing obesity and insulin resistance
[68].
The insulin concentrations also appear to be altered in accordance with the gut microbiota
[69]. Gut microbiota transplantation from lean subjects to patients with metabolic syndrome increased
insulin sensitivity [70]. This effect is probably related to the reduction of chronic low-grade
inflammation, resulting from LPS translocation and, consequently, to greater activation of the insulin
signaling cascade [71]. Like GLP-1, PYY is also produced by intestinal L cells in the form of PYY1-
36 and PYY3-36, the latter being present in higher concentrations in the postprandial period, causing
a sensation of satiety [72]. Obese individuals produced less PYY3-36, and no resistance to the
hormone was observed. Batterham et al. [73] found a 30% reduction in food intake 90 minutes after
the infusion of PYY3-36 in obese individuals, a value similar to eutrophic patients. The modulation of
the gut microbiota with prebiotic (oligofructose) of healthy subjects resulted in increased bacterial
fermentation, glucose tolerance, and reduced appetite from increased concentrations of GLP-1 and
PYY [74], probably due to a mechanism associated with the production of propionate by intestinal
bacteria [75]. Therefore, the gut microbiota is also related to the development of obesity, due to the
when compared to normal weight children [76,77], in overweight/obese women with metabolic
syndrome when compared with overweight/obese women with non-metabolic syndrome [78], and in
Japanese overweight individuals when compared with non-overweight individuals [79]. Furthermore,
the Firmicutes phylum has been shown to be negatively correlated with the resting energy expenditure
(REE) as well as positively correlated with fat mass percentage [80]. A cross-over clinical trial
observed that a 20% increase in the Firmicutes phylum abundance was associated with an increase of
150 kcal in energy harvest [81]. Finally, one study reported a decrease in the Firmicutes-to-
Obese individuals seem to have fewer Bacteroidetes counts than normal weight individuals
[79,82,83]. On the other hand, two studies associated the Bacteroidetes phylum with weight gain in
pregnant women [84,85]. A cross-over study with 29 subjects did not find differences in the
A decrease of Firmicutes was observed after Roux-en-Y gastric bypass (RYGB) [87,88] and
after laparoscopic sleeve gastrectomy (LSG) [89]. In contrast, Bacteroidetes counts increased after
RYGB and LSG [88, 89] but after a very low-calorie diet [89]. This phylum decreased with a
after diet therapy also was observed, and the Bacteroidetes proportion was positively correlated with a
The genera Staphylococcus [77,84,85,90,91] and Clostridium [84,85,89,92] have been shown
to be positively associated with obesity. A decrease in the genus Faecalibacterium was reported after
LSG [89], while the same genus increased after RYGB [93]. All these genera belong to the Firmicutes
phylum (Table 1). The Firmicutes phylum contains many butyrate producing species, and an increase
in butyrate and acetate synthesis may contribute to an increase in energy harvest in obese people
[15,94]. Furthermore, acetate can be absorbed and used as a substrate for lipogenesis and
The genus Bacteroides, which belongs to the phylum Bacteroidetes, was shown to have an
inverse relationship with obesity in overweight/obese women with metabolic disorder [78] after
RYGB [88,93] and LSG (Table 1) [89]. Bifidobacterium, which belongs to the phylum
Actinobacteria, was also shown to have an inverse relationship with obesity in pregnant women
[84,90], children [91], and infants of normal weight mothers [85]; however, this genus was decreased
in individuals subjected to RYGB [88,93]. Bifidobacterium species have been shown to deconjugate
bile acids, which may decrease fat absorption [95]. In contrast, strains of the same species can have
contradictory effects, as it has been shown that different Bifidobacterium strains might increase (strain
which leads to increased weight gain in mice [41]. A study demonstrated that humans with methane
detectable via a breath test have a significantly higher body mass index (BMI) than methane-negative
controls (Table 1). This implies a higher amount of M. smithii in obese individuals, which was not
Although several links have been reported between the gut microbiome and obesity (Table 2),
the mechanisms are not yet understood that explain how and when the microbiome affects the obese
state. Most studies investigating the relationships between obesity and the gut microbiome use very
small sample sizes and use a variety of analytical methods to infer the intestinal microbial
composition. Such factors are likely responsible for the considerable heterogeneity observed in the
results. For instance, different DNA extraction kits have an impact on the assessment of the human
Probiotics, prebiotics, and antibiotics have been evaluated, and they may become new
therapeutic possibilities for the treatment of obesity. Oral supplementation with probiotics seems to
reduce the concentrations of low-density lipoproteins (LDL) and total cholesterol; to ameliorate
atherogenic indices; to improve glycemic control [99]; to reduce body weight, waist
circumference, BMI, and abdominal visceral adipose tissue [100]; to improve body composition
[101], and to reduce the concentrations of pro-inflammatory markers such as interleukin 6 (IL-6)
and TNF-α[102]. Prebiotics also have been shown to contribute to weight loss and improve
metabolic parameters including insulin resistance [60]. Nevertheless, modulations performed with
probiotics show results only for specific strains and for the period evaluated, with little data available
regarding long-term benefits. In addition, the different ways in which different hosts can react to
supplementation make it impossible to carry out generalizations. In the future, the modulation of the
gut microbiota may be a way of assisting in the treatment of obesity, but for this idea to become a
reality, there is a need to understand the metabolic interactions between the modulated bacteria and
the host.
Conclusions
Although there is a large amount of heterogeneity in the data that is available, the following
conclusions can be drawn from the literature review: 1) obesity was characterized by the presence of
intestinal dysbiosis, marked by the distinct microbiome profile existing between obese and non-obese
individuals; 2) the resulting dysbiosis could change the functioning of the intestinal barrier and the
GALT, allowing the passage of structural components of bacteria, such as LPS, and activating
inflammatory pathways that may contribute to the development of insulin resistance by alteration of
insulin receptor signaling by the presence of inflammatory cytokines; 3) intestinal dysbiosis could
alter the production of gastrointestinal peptides related to satiety, resulting in an increased food intake
and contributing to a self-sustaining cycle; and 4) lipid metabolism could be altered by the changes
observed in the gut microbiome, resulting in a stimulus to increase body adiposity (Figure 1).
Understanding the changes occurring in the gut microbiome of obese individuals and the
physiological consequences of these changes is a necessary step in creating modulation strategies that
BMI: body mass index; BSH: bile salt hydrolase; CCL20: CC chemokine ligand 20; CCR6:
chemokine receptor 6; CLA: conjugated linoleic acid; C-X-C: chemokine; CXCL13: ligand 13
protein-coupled receptors; HBD3: β defensin 3 ligand; IFN- γ: interferon-γ; IL-6: interleukin 6; LBP:
LPS binding protein; LDL: low-density lipoproteins; LPS: lipopolysaccharides; LSG: laparoscopic
sleeve gastrectomy; LTi: lymphoid tissue inducer; MALT: mucosa-associated lymphoid tissue;
MyD88: myeloid differentiation factor 88; NF-κB: factor nuclear kappa B; NK: natural killer; NOD1:
PYY: peptide YY; RYGB: Roux-en-Y gastric bypass; SCFA: short chain fatty acids; TCR: T cell
receptor; TLR4: Toll-like 4 receptors; TLR5: Toll-like receptors 5; TLRs: Toll-like receptors; TNF:
Authors' contributions
ACG: drafted the manuscript and performed the design of the study. CH and JFM: drafted and revised
the manuscript. All authors read and approved the final manuscript.
Acknowledgements
Not applicable
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Table 1. Main results of studies that evaluated the gut microbiota composition in obesity.
Dietary intervention:
↓ acteroidetes; body
weight correlated
significantly positively
with Bacteroidetes and
negatively with
Firmicutes
To evaluate
associations
between
obesity and
microbiota
composition
, 14 lean
(BMI <25)
and 14
randomly
chosen
obese
subjects
(BMI >30)
were
selected
L. reuteri: was
associated with obesity
Post- important
Obese: roles in the
gastric 35.7 ±
bypass (n developmen
4.2 t of obesity
= 3) years and also to
determine
Post-
whether the
gastric
presence or
bypass:
43.3 ± abundance
8.1 of these
years microorgani
sms
changes
after
successful
post-gastric
bypass
surgery
Bacteroides/Prevotella
and E. coli: correlated
negatively with body
weight, BMI, body fat
mass, and serum leptin
concentrations
Bacteroides/Prevotella:
correlated negatively
with calorie intake
Normal weight:
↑Bacteroides
faecichinchillae;
↑Bacteroides
thetaiotaomicron;
↑Blautia wexlerae;
↑Clostridium bolteae;
↑Flavonifractor plautii
in obese and
normal
weight
individuals
LSG: laparoscopic sleeve gastrectomy; qPCR: quantitative polymerase chain reaction; FISH:
fluorescent in situ hybridization; FM: fat mass; HDL: high density lipoprotein
Table 2. Genus and species of bacteria and its relation to obesity.
Produces
cytotoxic
proteases:
[109]