ENDOCRINE CONSULT / PEER REVIEWED

The Gut Microbiome in Type 2 Diabetes

Clinician Reviews. 2018 February;28(2):13-14,16

References

1. Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell. 2012;148(6):1258-1270.
2. Barengolts E. Gut microbiota, prebiotics, probiotics and synbiotics in management of obesity and prediabetes: review of randomized controlled trials. Endod Prac. 2016;22(10):1224-1234.
3. Fujimura KE, Slusher NA, Cabana MD, Lynch SV. Role of the gut microbiota in defining human health. Expert Rev Anti Infect Ther. 2010;8(4):435-454.
4. Graessler J, Qin Y, Zhong H, et al. Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters. Pharmacogenomics J. 2013;13(6):514-522.
5. Larsen N, Vogensen F, van den Berg F, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PloS One. 2010;5(2):e9085.
6. Hartsra AV, Bouter KEC, Backhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015;38(1):159-165.
7. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022-1023.
8. Candela M, Biagi E, Soverini M, et al. Modulation of gut microbiota dysbioses in type 2 diabetic patients by macrobiotic Ma-Pi 2 diet. Br J Nutr. 2016;116(1):80-93.
9. Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262-266.

Bifidobacteria and lactobacilli are the most commonly used strains in foods and supplements containing probiotics. These live microorganisms bring about specific changes in the composition and activity of gut microbiota: they secrete antimicrobial substances, compete with pathogenic bacteria, strengthen the intestinal barrier, and modulate the immune system.^2,3,6 Research on human and animal models suggests that administering probiotics may help manage diabetes.²

DIETARY MODULATION

Dietary changes have been shown to modify the bacterial metabolic activity of the human gut. In one study, obese adults with T2DM were placed on either a fat- or carbohydrate-restricted diet, and it was found that their levels of Bacteroidetes increased and Firmicutes decreased.⁷

In another study, patients with T2DM adhered to one of two calorie-controlled diets: a high-fiber macrobiotic diet or a Mediterranean-style (control) diet. The macrobiotic diet was high in complex carbohydrates, legumes, fermented products, sea salt, and green tea and was free of animal protein, fat, and added sugar. Both diets were effective at improving dysbiosis—ecosystem diversity increased, and health-promoting SCFA producers were replenished. However, the macrobiotic diet was more effective than the control diet at reducing fasting and postprandial glucose, A1C, serum cholesterol, insulin resistance, BMI, and waist and hip circumferences; and only the macrobiotic diet counteracted the inflammation-producing bacterial groups.⁸

METFORMIN

Metformin has therapeutic effects on microbial composition and SCFA synthesis. In a microbiome comparison study, patients with T2DM treated with metformin had more butyrate-producing bacteria than their untreated counterparts. The trend toward increased Lactobacillus seen in the context of T2DM was reduced or reversed by metformin treatment. Researchers were able to tell which patients were (and were not) treated based on their gut microbiome taxonomic signature.⁹

FECAL MICROBIOTA TRANSPLANT

Fecal microbiota transplant, also known as stool transplant or bacteriotherapy, is the process of transferring fecal bacteria from a healthy individual into a recipient. It is used in the treatment of recurrent Clostridium difficile colitis to replenish beneficial bacteria in the digestive tract following use of wide-spectrum antibiotics. In a double-blind randomized controlled trial, insulin-resistant men received either autologous (reinfusion of one’s collected feces) or allogenic (feces from a lean donor) infusions. Allogenic transplantation resulted in significantly increased intestinal microbial diversity and increased levels of butyrate-producing species, accompanied by significantly improved peripheral muscle sensitivity to insulin.^1,6

BARIATRIC SURGERY

Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGBP), is a powerful tool used to treat obesity. In six patients (five of whom had diabetes) treated with RYGBP, dramatic changes to the gut microbiota were seen at three months following surgery. BMI was reduced by 15% to 32%, C-reactive protein decreased in five of six patients, and T2DM was alleviated in all. Postoperatively, there was a striking shift towards higher amounts of Proteobacteria and lower relative amounts of Firmicutes and Bacteroides in the gut phyla. Postoperative increases in certain bacteria were more profound than the amount in lean controls, suggesting these changes are related to alterations in the gut, not lower body weight.^4,6

CONCLUSION

We are just beginning to understand the microbiome and its relationship to health and disease. For patients with T2DM, a variety of interventions may be used to return the gut microbiota to health. Dietary interventions, prebiotics and probiotics, fecal microbial transplant, and bariatric surgery can influence gut microbial composition, with the goal of preventing and/or treating disease. In the future, gut microbial signatures may serve as early diagnostic markers.