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Table 1 Gut microbiota–obesity links based on experimental evidence (modified from Tuohy et al. 2009b)

From: Obesity and the gut microbiota: does up-regulating colonic fermentation protect against obesity and metabolic disease?

Model Design Evidence Proposed mechanism References
C57bl6/J Germ-free mice Conventionalization of wild-type and Fiaf −/−germ-free mice with murine gut microbiota or with Bacteroides tetaiotaomicron Conventionalization or monoassociation of germ-free mice led to increased body fat with less food intake compared with germ-free animals Gut microbiota suppression of Fiaf and relief of LPL inhibition and a resulting increased deposition of triglycerides in adipocytes Bäckhed et al. (2004)
C57bl6/J ob/ob mice Ob/ob versus lean wild-type cecal 16S rRNA gene fragment sequence A 50% reduction in the relative abundance of Bacteroidetes and a proportional increase in Firmicutes abundance in obese gut microbiota compared with the lean-type microbiota Lack of functioning leptin and resultant obesity-modified gut microbiota enhancing dietary energy recovery Ley et al. (2005)
Human adults 16S rRNA gene sequence library of gut microbiota in obese subjects on weight reduction diets (low carbohydrate or low fat, n = 12) Relative proportion of Bacteroidetes increased compared with Fimicutes and correlated with percentage of weight loss The gut in obesity exerts ecological pressure promoting a higher relative abundance of Firmicutes Ley et al. (2006)
Germ-free and ob/ob C57bl6/J mice Sequenced metagenome of cecal ob/ob and lean wild-type mice sequenced (n = 2) Increased Firmicutes and reduced Bacteroidetes prevalence in the obese compared with lean animals. ob/ob microbiome enriched in sequences encoding polysaccharide-degrading enzymes and other genes involved in energy recovery from diet The obese gut microbiota with enhanced potential to extract energy from diet Turnbaugh et al. (2006)
C57bl6/J Mice and CD14−/− mutant strain Metabolic, inflammatory and microbiological differences (FISH) between high-fat-fed obese or rodent lean chow-fed mice High-fat feeding and obesity decimates intestinal microbiota– Bacteroides-mouse intestinal bacteria, Bifidobacterium, and Eubacterium rectaleClostridium coccoides groups all significantly lower than in control animals High-fat diet-induced die-off of gut microbiota leads to elevated plasma LPS leading to metabolic endotoxemia, possibly through compromised mucosal barrier function Cani et al. (2007c)
C57bl6/J mice C57bl6/J mice-fed high-fat diet with or without the prebiotic oligofructose or cellulose, microbiota enumerated by FISH Prebiotic supplementation of high-fat diet stimulates bifidobacterial numbers, reduces metabolic endotoxemia and metabolic disease. Bifidobacterial numbers were inversely proportional to plasma LPS Prebiotics may reduce intestinal permeability and reduce metabolic endotoxemia via reduced plasma LPS Cani et al. (2007c)
Human adults Fecal bacterial composition of obese (n = 16) on different diets; maintenance, high-protein–medium carbohydrate, high protein/low carbohydrate. Microbiota enumerated by FISH Roseburia spp. and Eubacteium rectale subgroup, and bifidobacteria decrease with the high-protein/low-carbohydrate diet, accompanied by a decrease in fecal butyrate Gut microbiota and fecal butyrate concentrations change in relation to the presence of dietary fermentable carbohydrate Duncan et al. (2007)
C57bl6/J ob/ob mice Cecal microbiota of mice under high-fat low-fiber diet, and antibiotics. Microbiota enumerated by qPCR and DGGE Antibiotic reduced LPS cecal content in ob/ob and high fat
High-fat diet increased intestinal permeability and LPS uptake leading to metabolic endotoxemia
Obese/high-fat modified microbiota contributes to increased gut wall permeability and metabolic endotoxemia, which can be reversed by antibiotics Cani et al. (2008)
Human pregnant Comparison of the fecal microbiota (flow cytometry FISH, and qPCR) of overweight (n = 18) and normo-weight (n = 36) during first and third trimesters Bacteroides and Staphylococcusaureus were counted in higher numbers in overweight compared with normo-weight pregnant women Overweight can lead to aberrant gut microbiota during pregnancy inclining toward aberrant gut microbiota development in the infant and promoting subsequent obesity Collado et al. (2008)
Human adults Fecal microbiota difference (measured by FISH), between lean and obese, and obese upon weight loss No difference in Bacteroides populations between lean or obese, or upon weight loss in obese. Diet-correlated decrease in Firmicutes (Roseburia, E. rectale), and bifidobacteria in obese on weight loss Diets conceived for weight loss purpose of obese subject change the composition of gut-hosted microbiota Duncan et al. (2008)
Human children Retrospective study of fecal microbiota profile (FISH, flow cytometry, and qPCR) of infants presenting with either obesity or normal weight at age 7 years (25 out of 49) The obese children showed at infancy a fecal microbiota lower in bifidobacteria but higher in Staphylococcus aureus compared with infant who remained lean at 7 years Aberrant gut microbiota development during infancy contributes to obesity risk at childhood Kalliomaki et al. (2008)
Male Sprague–Dawley rats Induction of excess of body weight in pups in over-nutrition and normal nutrition condition with microbiota enumerated by FISH and plate count Obesity resulted from overfed small litters who had reduced Bacteroides and increased enterococci and lactobacilli compared with normo-weight, conventionally housed and fed animals Postnatal nutrition has obesity-inducing potential by impacting the gut microbiota development Mozes et al. (2008)
Germ-free C57BL/6 J mice Conventional under Western-style or high-carbohydrate diets and conventionalized with obese-type microbiota from Western-style or high-carbohydrate diets. The colon microbiota was examined by PCR-based 16S rRNA gene fragment sequencing and functional analysis Western-style diet and associated obesity induced Firmicutes bloom characterized by increased abundance of in a single phylogenetic clade within the Mollicutes class; relative abundance of Bacteroidetes decreased. Conventionalization of lean germ-free mice with Mollicutes-dominated microbiota lead to higher body weight gain than with lean-type microbiota. Western diet/Mollicutes-modulated microbiota have a higher capacity for intake and fermentation of simple sugars Western-style diet selects for a particular gut microbiota with increased capacity for energy recovery from diet Turnbaugh et al. (2008)
Human adults qPCR analysis of the gut microbiota of obese, anorexic, and lean human adults Lower Bacterioidetes in obese patients and obese microbiota enriched in Lactobacillus Gut microbiota displays distinct pattern in obesity Armougom et al. (2009)
Mice Wild-type and RELMβ KO mice from a normal to a high-fat diet. Microbial evaluation by 16S rDNA deep sequencing using 454 Gut microbiota from normal diet (Bacterioidetes more abundant than Firmicutes, mostly Clostridia genus with lower abundance of Tenericutes, Proteobacteria) shifted after high-fat diet to higher proportion of Firmicutes (mostly Clostridiales) and lower Bacteriodetes (Bacteriodacee, Prevotellaceae, Rickenellaceae, the more affected orders) together with a bloom of Proteobacteria (Desulfuvibrionaceae)
Change also in amino acid and carbohydrate metabolism, which were less abundant after high-fat feeding
Impact of dietary fat on the gut microbiota composition and metabolism: changes induced by obesity or direct from fat Hildebrandt et al. (2009)
Human adolescents Fecal microbiota (FISH and IgA-coating bacteria) of obese adolescents before and after restricted calorie diet and physical activity regime (n = 39, 10 weeks) C. histolyticum, E. rectale-C. coccoides groups decreased count with weight loss; Bacteroides-Prevotella increased upon weight loss of >4 kg;
IgA-coating bacteria decreased in those who lost >6 kg
Potential link between diet, gut microbiota, immunity, and host metabolic processes involved in obesity Nadal et al. (2009)
Human adolescents Fecal microbiota (qPCR) of overweight adolescents (n = 36) under calorie-restricted diet and physical activity Total bacterial were higher, as were Bacterioides fragilis and Clostridium leptum and Bifidobacterium catenulatum in the obese population in which intervention was more effective. C. coccoides, Lactobacillus, Bifidobacterium, B. bifidus, and B. breve were lower. The weight loss dietary intervention affected also B. longum Differences in the gut microbiota are correlated with a high effective response to weight loss inducing intervention Santacruz et al. (2009)
Humans adults Intestinal microbiota (qPCR) and feces SCFA of lean (n = 30), overweight (n = 35), and obese (n = 33) humans Higher proportion of Bacterioidetes in overweight and obese. Ruminococcus flavefaciens subgroup reduced in overweight and obese Clostridium leptum group, Methanobrevibacter and Bifidobacterium all reduced in overweight and obese
Higher amount of SCFA in obese, more propionate in overweight and obese
SCFA concentration elevated in obese feces with significant differences in the composition of gut microbiota between lean and obese at phylum and sub-phylum levels Schwiertz et al. (2010)
Human female twins and their mothers Adult female monozygotic and dizygotic twin pairs concordant for obesity and their mothers (n = 31, 23 and 46, respectively)
Gut microbiota described by 16s rRNA gene sequencing
Lower abundance of Bacteroidetes, but higher Actinobacteria (no change in Firmicutes) in obese. Reduced species diversity in obese. Metabolic pathways and functional genes altered in obesity. Functional heterogeneity associated with the relative amount of Bacteroidetes. Microbiota enriched in Firmicutes/Actinobacteria exhibited more less diverse functions Modulated functional microbiome with metagenomic differences in carbohydrate, lipid, and amino acid metabolism Turnbaugh et al. (2009a)
Zucker fa/fa, fa/+ and +/+ rats Cecal microbiota composition (FISH and DGGE) in Zucker genotypes on normal diet correlated with 1H-NMR metabolomics of urine and blood Microbiota of obese fa/fa animals distinct from non-obese genotypes. Total bacteria, bifidobacteria, lactobacilli, and Atopobium species, all significantly lower in obese ceca. Distinct urine and plasma metabolite profiles associated with obesity and obese-type microbiota Gut microbiota of the Zucker genetic model of obesity linked to energy metabolism and obesity in these animals Waldram et al. (2009)
Humans post-gastric bypass (PGB) surgery Fecal microbiota from 3 lean, 3 morbidly obese, and 3 PGB surgery patients upon weight loss describe after PCR-based 16S rRNA gene fragment sequencing and qPCR for methanogens Bacterioidetes (Prevotellaceae) more abundant in obese Firmicutes dominant in lean and obese but reduced in PGB, PGB had increased Gammaproteobacteria
Methanogenic functional group elevated in obese
Increased methanogenesis, enhancing fermentation through relief of end-product inhibition increases production of acetate absorbed at the human gut contributing to enhanced energy recovery Zhang et al. (2009)
Human children Obese and non-obese Indian children (11–14 years: n: 28) fecal microbiota enumerated by 16S rRNA target by qPCR Bacterioides-Prevotella, Lactobacillus acidophilus, Eubacterium rectale were not significantly different in obese and non-obese. High number of Faecalibacterium prausnitzii characterized the obese children Evident alteration of gut microbiota in obese children Balamurugan et al. (2010)
Sprague–Dawley rat Obesity-prone (DIO-P) and resistant (DIO-R) rats under high-fat diet were examined for 16S rRNA qPCR microbiota, TLR4, and LPS Reduced total bacterial count with higher relative proportions of Bacterioidales and Clostridiales after high-fat feeding. Greater abundance of Enterobacteriales in DIO-P
Increased intestinal permeability and plasma LPS upon high-fat feeding
Change in microbiota induced by high-fat diet and inflammation development associated with obesity de La Serre et al. (2010)
Germ-free (GF) and conventional (CV) mice Fecal microbiota and Fiaf/Angptl4 in GF and CV male adult mice on low-fat diet (LFD), a high-fat diet (HFD), or a commercial Western diet (WD) Bacteroidetes relative amount was lower in on both HFD and WD in favor of Firmicutes. One species of Firmicutes was predominated: the Erysipelotrichaceae
Higher expression of Fiaf/Angptl4 at intestinal level in HFD and WD
Concluded that the absence of gut microbiota does not provide a general protection from diet-induced obesity, that intestinal production of intestinal Fiaf/Angptl4 and gut microbiota are not linked together in fat storage. Diet composition highly affects gut microbiota Fleissner et al. (2010)
C57bl6/J ob/ob mice Feces of ob/ob (low-fat diet) compared to wild type (low-fat and high-fat diet HF) for their metagenomic profile (16S rRNA tags pyrosequencing) in relation to low-fat and high-fat diet. SCFA analysis Firmicutes more abundant in ob/ob and HF wild mice. Bacteriodes significantly decrease in ob/ob. Actinobacteria increased in ob/ob and HF mice from 7 to 11 weeks. Protobacteria decline in HF mice. Bifidobacteria decline in ob/ob and HF at 11 weeks
SCFA concentrations and fecal energy content higher in obese at week 7 but lower upon adaptation to diet
High-fat diet may have more influence gut microbiota composition than host genotype. Diet and obesity-induced changes in microbiota energy harvesting change upon adaptation to high-fat diet Murphy et al. (2010)
Human pregnant Feces from overweight (n 16) and normal weight (n 34) pregnant women analyzed by qPCR, together with monitoring of body weight and biochemical parameters from plasma Overweight women had more abundant fecal Enterobacteriacee, E. coli, and Staphylococcus and lower counts of Bifidobacterium and Bacterioidetes in comparison with normal weight subjects. A. muciniphila and Bifidobacterium were higher in subjects with normal weight gain, compared with those with excessive weight gain. C. leptum and Staphylococcus counts correlated with excessive weight gain. Higher amount of folic acid and Fe in normal weight subject Gut microbiota associated with body weight and body weight gain, pregnancy important metabolites, beneficial health effect on woman and infant Santacruz et al. (2010)
Mice Wild-type and Apoa-I knocked out mice intolerant to glucose, under fat or normal diet, DGGE-DNA fingerprint and 16S rRNA pyrosequencing Bifidobacteriacea disappeared after high-fat diet and Desulfovibrionacea prevailed in the glucose impaired/obese group High impact of diet on the microbiota composition, potentially capable to induce metabolic syndrome Zhang et al. (2010)