The human gut microbiota: Metabolism and perspective in obesity

Figures & data

Table 1. Main results of studies that evaluated the gut microbiota composition in obesity.

Ref	Subjects’ characteristics	Age	Design	Objective	Methods of detection	Results	Quality
84	Overweight pregnant women (n = 18)	Overweight: 30.0 years (26.4–34.0)	Case-control	To characterize the gut microbiota in women according to their body mass index (BMI) and the effect of weight gain over pregnancy on the composition of microbiota before delivery	FISH and qPCR	Overweight: ↑ Bacteroides, Staphylococcus aureus and Clostridium	B
	Normal weight (n = 36)	Normal weight: 30.5 years (26.6–33.6)				Bacteroides: positive correlation with weight and BMI before pregnancy and weight gain over pregnancy
						Bifidobacterium : ↑ in women with lower weight gain over pregnancy
91	Overweight and obese children (n = 25)	7 years	Cross-sectional	To establish whether early gut microbiota composition can guide weight development throughout early childhood	FISH and qPCR	Overweight: ↑ Staphylococcus aureus	B
	Normal weight (n = 24)					Normal weight: ↑ Bifidobacterium numbers
85	Mothers and their infants.	Pre-pregnancy overweight: 28.55 years (26.2–34.12)	Cross-sectional	To analyze the fecal microbiota composition of infants with overweight and normal weight mothers and to assess the relationship of weight and excessive weight gain of mothers during pregnancy on the microbiota of infants	FISH and qPCR	Infants of overweight mothers: ↓Bacteroides-Prevotella; ↑Clostridium histolyticum; ↑Staphylococcus aureus; ↑Akkermansia muciniphila; ↑Akkermansia	B
	Pre-pregnancy body mass index >25 (n = 16) or normal weight (n = 26)	Normal weight: 30.04 years (26.43–33.70)				Infants of normal weight mothers: ↑Bifidobacterium; ↓Bifidobacterium adolescentis
		Infants: 1–6 months				Infants of mothers with excessive weight gains: ↓Bacteroides-Prevotella; ↑Clostridium histolyticum; ↓Bifidobacterium; ↑Staphylococcus aureus
88	N = 30 morbidly obese women enrolled in a bariatric surgery program	—	Clinical trial	To examine the impact of Roux-en-Y gastric bypass (RYGB) on modifications of gut microbiota and its potential associations with changes in gene expression in white adipose tissue	Multiplex pyrosequencing	After RYGB: ↑richness of gut microbiota; ↓Firmicutes (Lactobacillus, Dorea, and Blautia); ↓Bifidobacterium; ↑Bacteroidetes (Bacteroides and Alistipes); ↑Escherichia	B
77	Overweight and obese children and adolescents (n = 26)	Overweight and obese: 11.64 ± 2.43 years	Cross-sectional	To investigate and compare the gut microbiota composition in obese and lean children	qPCR and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry	Obese: ↑Firmicutes-to-Bacteroidetes ratio; ↑Lactobacillus spp; ↓Bacteroides vulgatus	B
	Normal weight (n = 27)	Normal weight: 10.70 ± 3.12 years				Lactobacillus spp.: positively associated with plasma hs-CRP
						Staphylococcus spp.: positively associated with energy intake
	N = 12 obese people	(21–65)	Clinical trial	To investigate the relationship between gut microbial ecology and body fat in humans	qPCR	92.6% of gut microbiota (obese): Bacteroidetes and Firmicutes	B
15	Fat-restricted low-calorie diet (FAT-R) (n = 6)					Before diet therapy: ↓Bacteroidetes; ↑Firmicutes
	Carbohydrate-restricted low-calorie diet (CARB-R) (n = 6)					After diet therapy: ↑Bacteroidetes; ↓Firmicutes
						↑Bacteroidetes: positively correlated with percentage loss of body weight
80	Obese (n = 50)	Obese: 51.9 years (48.1–55.7)	Cross-sectional	To assess the composition of gut microbiota and its association with resting energy expenditure (REE) in obese and normal weight subjects	Semi-quantitative analysis of gut microbiota composition in aerobic and anaerobic conditions	Bacteroides-to-Firmicutes rate was similar in both study groups	B
	Normal weight (n = 30)	Normal weight: 42.6 years (38.1–47.1)				Positive correlation between:
						REE (kcal/day) and total bacterial count
						REE (kcal/m^2/h) and total bacterial count
						Firmicutes count and percentage of fat mass
						Negative correlation between:
						REE (kcal/day) and percentage of Firmicutes
						REE (kcal/m^2/h) and percentage of Firmicutes
89	Obese women who underwent laparoscopic sleeve gastrectomy (LSG) (n = 5) or dietary weight loss regimen (n = 5)	48 ± 3 years	Longitudinal pilot clinical trial	To investigate functional weight loss mechanisms with regard to gut microbial changes and energy harvest induced by LSG and a very lowcalorie diet	SOLiD long-mate-paired shotgun sequencing	LSG: ↑Bacteroidetes and ↓Firmicutes (Clostridium, Eubacterium, Faecalibacterium, Dorea, and Coprococcus); ↑Butyrivibrio fibrisolvens; ↑Clostridium saccharolyticum; ↑Eubacterium; ↑Blautia hydrogenotrophica; Bacteroidetes showed a negative correlation with body weight; Firmicutes were positively correlated with body weight	B
						Dietary intervention: ↓Bacteroidetes; body weight correlated significantly positively with Bacteroidetes and negatively with Firmicutes
103	African Americans (n = 42)	African Americans: 51.2 years	Cross-sectional	To investigate if differences in dietary habits between the two groups are associated with cytotoxicity/ genotoxicity of fecal water and with fecal microbiota composition	FISH and qPCR	↑ Calories from fat: ↓Clostridium;	B
	Caucasian Americans (n = 40)	Caucasian Americans: 52.3 years		To evaluate associations between obesity and microbiota composition, 14 lean (BMI <25) and 14 randomly chosen obese subjects (BMI >30) were selected		↑ Dietary fiber: ↑lactic acid bacteria;
						BMI was not associated with proportions of Bacteroides or Firmicutes
83	Obese (n = 68)	Obese: 50.5 ± 14.4 years	Cross-sectional	To test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status	qPCR	Obese: ↑Lactobacillus reuteri; ↑Lactobacillus; E. coli	A
	Control (n = 47)	Control: 42.6 ± 17.5 years				Control: ↑Lactobacillus paracasei; Lactobacillus plantarum;
						Methanobrevibacter smithii, Bifidobacterium animalis
						B. animalis : was associated with normal weight
						L. reuteri : was associated with obesity
78	Overweight/obese women in metabolic disorder group (MDG, n = 27) or in non-metabolic disorder group (NMDG, n = 47) or normal weight women group (NWG, n = 11)	MDG: 42 ± 8 years	Cross-sectional	To investigate whether overweight/obese women in MDG differ in their gut microbiota composition from overweight/obese women in NMDG and NWG	FISH	MDG: ↑E.rectale-C.coccoides, ↑gram-negative, ↑Erec-to-Bacto ratio, ↑Firmicutes/Bacteroidetes ratio	A
		NMDG: 39 ± 9 years				E. rectale-C. coccoides group: positive correlation with ↑body weight, BMI, FM, FM%, visceral fat area, and serum triglycerides; negative correlation with HDL concentrations
		NWG: 31 ± 14 years				Bacteroides: inverse correlation with body weight, BMI, FM, FM%, and insulin concentration; positive correlation with HDL
92	Obese (n = 33)	43 ± 13.85 years	Clinical trial	To identify bacteria affecting host metabolism in obesity during weight loss and to correlate them with changes in body composition	qPCR	After weight reduction: ↑ total bacterial abundance, Lactobacillus, Akkermansia; ↓ ratio of Firmicutes/Bacteroidetes, Clostridium;	A
						Differences in lactobacilli abundance correlated with differences in weight percentage
90	Pregnant women (24 weeks of pregnancy)	Overweight: 29 years (28.0–33.5)	Cross-sectional	To establish possible relationships between gut microbiota, body weight, weight gain, and biochemical parameters in pregnant women	qPCR	Obese women: ↑Enterobacteriaceae; ↑Escherichia coli; ↑Staphylococcus	B
	Overweight (n = 16)	Normal weight: 31 years (27.7–34.2)				Normal weight: ↑Bifidobacterium; ↑ratio of Bifidobacterium to C. coccoides group
	Normal weight (n = 34)					Excessive weight gain: ↑ Escherichia coli; ↑C. leptum; ↑Staphylococcus ↓Akkermansia muciniphila; ↓Bifidobacterium
104	Overweight adolescents randomized in low weight loss group (n = 13) or high weight loss group (n = 23) Intervention based on an energy-restricted diet and regular physical activity	14.5 years (13.0–15.0)	Clinical trial	To determine the influence of an obesity treatment program on the gut microbiota and body weight of overweight adolescents	qPCR	Both: ↑Bacteroides fragilis; ↑Lactobacillus; ↓Clostridium coccoides; ↓Bifidobacterium longum; ↓Bifidobacterium adolescentis	A
						Bacteroides fragilis and Clostridium leptum : positively correlated with higher weight loss
						Escherichia coli, Clostridium coccoides, Lactobacillus and Bifidobacterium : negatively correlated with higher weight loss
						B. breve and B. bifidum : correlated with lower weight loss
82	Obese (n = 20)	Obese: 17–72 years	Cross-sectional	To assess the relative abundance of Lactobacillus, Methanobrevibacter smithii, Bacteroidetes, and Firmicutes divisions in the microbiota of obese, lean, and patients with anorexia nervosa	qPCR	Obese: ↓Bacteroidetes; ↑Lactobacillus	B
	Anorexia nervosa (n = 9)	Anorexia: 19–36 years				The anorexic bacterial profile is similar to the lean control group
	Normal weight (n = 20)	Normal weight: 13 –68 years
86	15 obese male subjects and 14 non-obese subjects	—	Cross-over clinical trial	To examine the relationships between BMI, weight loss, and the major bacterial groups detected in fecal samples	FISH	Bacteroides: No difference between obese and non-obese individuals	B
	4 weeks: high-protein low carbohydrate					No relationship between changes in the percentage of Bacteroides and weight lost
	4 weeks: high-protein moderate carbohydrate					After diet: ↓Roseburia+Eubacterium rectale; ↓Bifidobacteria; no change in the percentage of Firmicutes; no change in the percentage of Bacteroidetes
87	Normal weight (n = 3)	Normal weight: 36.7 ± 4.0 years	Cross-sectional	To identify specific microbial lineages that may play important roles in the development of obesity and also to determine whether the presence or abundance of these microorganisms changes after successful post-gastric bypass surgery	qPCR	Obese: ↑Prevotellaceae; ↑Archaea; ↑Firmicutes	B
	Obese (n = 3)	Obese: 35.7 ± 4.2 years				Post-gastric bypass: ↓Firmicutes, ↑Gammaproteobacteria
	Post-gastric bypass (n = 3)	Post-gastric bypass: 43.3 ± 8.1 years
93	Normal weight (n = 13)	—	Cross-sectional analyses: before (M0), 3 months (M3), and 6 months (M6) after Roux-en-Y gastric bypass	To analyze the impact of RYGB on the modifications of gut microbiota and to examine links with adaptations associated with this procedure	qPCR	Obese M0: ↓ Bacteroides/Prevotella; ↓F. prausnitzii	B
	Obese (n = 30)					Obese M3: ↑Bacteroides/Prevotella; ↑Escherichia coli; ↑ Faecalibacterium prausnitzii; ↓Bifidobacterium; ↓Lactobacillus/Leuconostoc/Pediococcus groups;
						F. prausnitzii : negatively correlated with inflammatory markers
						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
81	Normal weight (n = 12)	Normal weight: 32.8 ± 9.2 years	Cross-over clinical trial	To test how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota is correlated with the efficiency of dietary energy harvest	Multiplex pyrosequencing	97%: Firmicutes + Bacteroidetes	A
	Obese (n = 9)	Obese: 35.8 ± 10.6 years				↑20% in Firmicutes and ↓ Bacteroidetes: energy harvest of ≈150 kcal
83	Obese (n = 134)	Obese: 51.8 ± 14.7 years	Cross-sectional	To analyze the fecal concentrations of Bacteroidetes, Firmicutes, Methanobrevibacter smithii, the genus Lactobacillus, and five other Lactobacillus species previously linked with lean or obese populations	PCR	Obese: ↑Lactobacillus; ↑Lactobacillus reuteri; ↓Bacteroidetes; ↓M. smithii; ↓Bifidobacterium animalis; ↓E. coli	A
	Overweight (n = 38)	Overweight: 54.1 ± 17.8 years				Overweight: ↑L. reuteri
	Normal weight (n = 76)	Normal weight: 49.5 ± 18.6 years				Positive correlation between: L. reuteri and BMI
	Anorexic patients (n = 15)	Anorexic patients: 27.3 ± 10.8				Negative correlation between: M. smithii and BMI; E. coli and BMI
79	Overweight (n = 33)	Overweight: 54.4 ± 8.2 years	Cross-sectional	To examine the human gut microbiota composition in a Japanese population	Next generation sequencing	Overweight:	B
	Normal overweight (n = 23)	Normal weight: 45.6 ± 9.6 years				↓Bacteroidetes; ↑Firmicutes-to-Bacteroidetes ratio; ↑Microbial diversity; ↑Blautia hydrogenotorophica; ↑Coprococcus catus; ↑Eubacterium ventriosum; ↑Ruminococcus bromii; ↑Ruminococcus obeum
						Normal weight: ↑Bacteroides faecichinchillae; ↑Bacteroides thetaiotaomicron; ↑Blautia wexlerae; ↑Clostridium bolteae; ↑Flavonifractor plautii
76	Obese (n = 42)	6–16 years	Cross-sectional	To characterize the composition of the gut microbiota in obese and normal weight individuals	PCR	Obese: ↓Bacteroidetes; ↑Firmicutes; ↑Firmicutes-to-Bacteroidetes ratio	B
	Normal weight (n = 36)

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.

Species	Genus	Phylum	Characteristics	In obese individuals	Effect associated with obesity
—–	Bacteroides	Bacteroidetes	gram -; anaerobic; non-spore-forming	↓ Except in pregnant women	↓absorption of dietary fat^Citation105; GALT development^Citation106
Bacteroides vulgatus	Bacteroides	Actinobacteria	gram -; anaerobic; non-spore-forming	↓	Part of the core gut microbiota in healthy humans^Citation14
Bacteroides fragilis	Bacteroides	Bacteroidetes	gram -; anaerobic; non-spore-forming	↓	↑IL-10 production^Citation107
Staphylococcus aureus	Staphylococcus	Firmicutes	gram +; facultative anaerobe; non-spore-forming	↑	Trigger of low-grade inflammation^Citation91
——	Clostridium	Firmicutes	gram +; anaerobic; spore-forming	↑	↑Energy storage; ↑low-grade inflammation^Citation85
Clostridium histolyticum	Clostridium	Firmicutes	gram +; facultative anaerobe; produces endospores	↑	Produces acetate, that ↑lipid synthesis^Citation108
					Produces cytotoxic proteases:^Citation109
Akkermansia muciniphila	Akkermansia	Verrucomicrobia	gram -; anaerobic; non-spore-forming; mucin-degrading bacterium	↑ Except in pregnant women	↑Degradation of intestinal mucin; ↑pro-inflammatory activity^Citation85
Escherichia coli	Escherichia	Proteobacteria	gram -; facultative anaerobe; non-spore-forming	Disputed	The absence of E. coli was an independent predictor of weight gain^Citation83; ↑harvest energy^Citation88
L. reuteri	Lactobacillus	Firmicutes	gram +; anaerobic; non-spore-forming	↑	↑Gut's ability to absorb and process nutrients^Citation110
L. plantarum	Lactobacillus	Firmicutes	gram +; anaerobic; non-spore-forming	↓	↑Conjugated linoleic acid, which increases energy expenditure and produces an anti-obesity effect^Citation111
——	Bifidobacterium	Actinobacteria	gram +; anaerobic; non-spore-forming	Disputed	↑Insulin resistance, adiponectin ↓Inflammatory adipokine expressions ↑Conjugated linoleic acid^Citation112
Bifidobacterium adolescentis	Bifidobacterium	Actinobacteria	gram +; anaerobic; non-spore-forming	↓	↓Visceral fat accumulation; ↑Insulin sensitivity^Citation113
Butyrivibrio fibrisolvens	Butyrivibrio	Firmicutes	gram +; anaerobic; non-spore-forming	↓	↑Conjugated linoleic acid^Citation114
Faecalibacterium prausnitzii	Faecalibacterium	Firmicutes	gram +; anaerobic; non-spore-forming	↓	Modulates systemic inflammation^Citation115
E.rectale-C.coccoides	Eubacterium / Clostridium	Firmicutes	gram +; anaerobic; non-spore-forming/spore-forming	↑	↑Butyrate; ↑Harvest energy from the diet^Citation116

Figure 1. Possible mechanisms that related the obesity and intestinal dysbiosis with the physiological changes that contributed to the maintenance of obesity. GALT: gut-associated lymphoid tissue; IgA: immunoglobulin A; LPS: lipopolysaccharide; NF-κB: nuclear factor kappa B; CLA: conjugated linoleic acids; PPAR: peroxisome proliferator-activated receptor; LPL: lipoprotein lipase; Angptl4: angiopoietin like protein 4; GLP-1: glucagon-like peptide 1; PYY: peptide YY.

Gauffin Cano P, Santacruz A, Moya Á, Sanz Y. Bacteroides uniformis CECT 7771 ameliorates metabolic and immunological dysfunction in mice with high-fat-diet induced obesity. PLoS One. 2012;7:e41079. doi:10.1371/journal.pone.0041079. PMID:22844426.

 PubMed Web of Science ®Google Scholar

Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL. Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol. 2004;172:1118–24 doi:10.4049/jimmunol.172.2.1118. PMID:14707086.

 PubMed Web of Science ®Google Scholar

Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65. doi:10.1038/nature08821. PMID:20203603.

 PubMed Web of Science ®Google Scholar

Ochoa-Reparaz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010;3:487–95. doi:10.1038/mi.2010.29. PMID:20531465.

 PubMed Web of Science ®Google Scholar

Kalliomaki M, Collado MC, Salminen S, Isolauri E. Early differences in fecal microbiota composition in children may predict overweight. Am J Clin Nutr. 2008;87:534–8. doi:10.1093/ajcn/87.3.534. PMID:18326589.

 PubMed Web of Science ®Google Scholar

Collado MC, Isolauri E, Laitinen K, Salminen S. Effect of mother's weight on infant's microbiota acquisition, composition, and activity during early infancy: a prospective follow-up study initiated in early pregnancy. Am J Clin Nutr. 2010;92:1023–30. doi:10.3945/ajcn.2010.29877. PMID:20844065.

 PubMed Web of Science ®Google Scholar

Collins MD, Lawson PA, Willems A, Cordoba JJ, Fernandez-Garayzabal J, Garcia P, Cai J, Hippe H, Farrow JA. The phylogeny of the genus Clostridium: proposal of five new genera and eleven new species combinations. Int J Syst Bacteriol. 1994;44:812–26. doi:10.1099/00207713-44-4-812. PMID:7981107.

 PubMedGoogle Scholar

De Graaf AA, Venema K. Gaining insight into microbial physiology in the large intestine: a special role for stable isotopes. Adv Microb Physiol. 2008;53:73–168. PMID:17707144.

 PubMed Web of Science ®Google Scholar

Million M, Thuny F, Angelakis E, Casalta JP, Giorgi R, Habib G, Raoult D. Lactobacillus reuteri and Escherichia coli in the human gut microbiota may predict weight gain associated with vancomycin treatment. Nutr Diabetes. 2013;3:e87. doi:10.1038/nutd.2013.28. PMID:24018615.

 PubMed Web of Science ®Google Scholar

Kong L, Tap J, Aron-Wisnewsky J, Pelloux V, Basdevant A, Bouillot J, Zucker J, Doré J, Clément K. Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes. Am J Clin Nutr. 2013;98:16–24. doi:10.3945/ajcn.113.058743. PMID:23719559.

 PubMed Web of Science ®Google Scholar

Casas IA, Dobrogosz WJ. Validation of the probiotic concept: Lactobacillus reuteri confers broad-spectrum protection against disease in humans and animals. Microb Ecol Health Dis. 2000;12:247–85. doi:10.1080/08910600050216246-1.

 Google Scholar

Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, Paek KS, Lee Y, Park JH. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta. 2006;1761:736–44. doi:10.1016/j.bbalip.2006.05.007. PMID:16807088.

 PubMed Web of Science ®Google Scholar

Le TK, Hosaka T, Le TT, Nguyen TG, Tran QB, Le TH, Pham XD. Oral administration of Bifidobacterium spp. improves insulin resistance, induces adiponectin, and prevents inflammatory adipokine expressions. Biomed Res. 2014;35:303–10. doi:10.2220/biomedres.35.303. PMID:25355437.

 PubMed Web of Science ®Google Scholar

Chen J, Wang R, Li XF, Wang RL. Bifidobacterium adolescentis supplementation ameliorates visceral fat accumulation and insulin sensitivity in an experimental model of the metabolic syndrome. Br J Nutr. 2012;107:1429–34. doi:10.1017/S0007114511004491. PMID:21914236.

 PubMed Web of Science ®Google Scholar

Fukuda S, Furuya H, Suzuki Y, Asanuma N, Hino T. A new strain of Butyrivibrio fibrisolvens that has high ability to isomerize linoleic acid to conjugated linoleic acid. J Gen Appl MicroBiol. 2005;51:105–13 doi:10.2323/jgam.51.105. PMID:15942871.

 PubMed Web of Science ®Google Scholar

Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome Med. 2016;8:42. doi:10.1186/s13073-016-0303-2. PMID:27098727.

 PubMed Web of Science ®Google Scholar

Flint HJ, Duncan SH, Scott KP, Louis P. Interactions and competition within the microbial community of the human colon: links between diet and health. Environ MicroBiol. 2007;9:1101–11. doi:10.1111/j.1462-2920.2007.01281.x. PMID:17472627.

 PubMed Web of Science ®Google Scholar