Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes
Purpose of Review
Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.
Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation.
While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.
KeywordsMicrobiome Obesity Metabolic syndrome Diabetes Inflammation Endotoxin
Compliance with Ethical Standards
Conflict of Interest
Xinpu Chen and Sridevi Devaraj declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Obesity Expert Panel. Executive summary: guidelines (2013) for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association task force on practice guidelines and the Obesity Society published by the Obesity Society and American College of Cardiology/American Heart Association task force on practice guidelines. Based on a systematic review from the obesity expert panel, 2013. Obesity (Silver Spring). 2013;2014(Suppl 2):S5–39.Google Scholar
- 7.Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev. 2000;6:776–88.Google Scholar
- 15.•• Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027–31 This was one of the pioneering studies to demonstrate that the gut microbiota from obese can harvest increased energy from diet and thus contribute to the pathophysiology of obesity. CrossRefPubMedGoogle Scholar
- 17.•• Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214 Studies in this report emphasize the strong microbiota-by-diet interactions and illustrate how a poor diet (high saturated fat and low in fruits and vegetables) can select against human gut bacterial taxa associated with lean body mass. CrossRefPubMedGoogle Scholar
- 26.Verma S, Hussain ME. Obesity and diabetes: an update. Diabetes Metab Syndr. 11(1):73–79.Google Scholar
- 30.•• Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56:1761–72 One of the first studies that demonstrates that increased endotoxin results in increased inflammation, weight gain and diabetes. CrossRefPubMedGoogle Scholar
- 40.Rempel JD, Packiasamy J, Dean HJ, McGavock J, Janke A, Collister M, et al. Preliminary analysis of immune activation in early onset type 2 diabetes. Int J Circumpolar Health. 2013;5:72.Google Scholar
- 48.Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–5.CrossRefPubMedGoogle Scholar
- 53.De la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, Velásquez-Mejía EP, Carmona JA, Abad JM, et al. Metformin is associated with higher relative abundance of mucin-degrading Akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care. 2017;40:54–62.CrossRefPubMedGoogle Scholar
- 54.• Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528:262–6 Provides evidence of microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production. Overall, the study emphasizes the need to disentangle gut microbiota signatures of T2DM from those that receive metformin and other antidiabetic medication. CrossRefPubMedPubMedCentralGoogle Scholar
- 56.Aron-Wisnewsky J, Prifti E, Belda E, Ichou F, Kayser BD, Dao MC, Verger EO, Hedjazi L, Bouillot JL, Chevallier JM, Pons N, Le Chatelier E, Levenez F, Ehrlich, SD, Dore J, Zucker JD, Clément K. major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut. 2018.Google Scholar
- 57.Duboc H, Nguyen CC, Cavin JB, Ribeiro-Parenti L, Jarry AC, Rainteau D, et al. Roux-en-Y gastric-bypass and sleeve, gastrectomy induces specific shifts of the gut microbiota without altering the metabolism of bile acids in the intestinal lumen. Int J Obes (Lond). 2018. https://doi.org/10.1038/s41366-018-0015-3.