Volume 2 | Issue 2 | 2015-12-14

Gut Microbiota and Glucose Homeostasis

Katsunori Nonogaki

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The involvement of gut microbiota in type 2 diabetes has been recognized [1,2] . Several Clostridium or lactobacilli species are reportedly enriched in type 2 diabetes [1,2] . A study by Forslund et al, showed that gut microbes mediate the therapeutic effects of metformin through certain types of short-chain fatty acid production [3] . Gut microbiota may therefore influence insulin sensitivity. Serum metformin levels of type 2 diabetes patients are positively correlated with Escherichia abundance, whereas they are negative correlation with Intestinibacter abundance [3] . Serotonin (5-hydroxytryptamine, 5-HT) is mainly synthesized, stored, and released from enterochromaffin cells within mucosal epithelia of the gut [4] . Gut microbes regulate 5-HT levels in the colon and blood. Spore-forming bacteria (Sp) from the mouse and human microbiota promote 5-HT biosynthesis from colonic enterochromaffin cells, which supply 5-HT to the mucosa, lumen, and circulating platelets [4] . The microbiota-dependent changes in gut 5-HT impact gastrointestinal motility and platelet function [4] . 5-HT1B and 5-HT4 receptors, which are distributed in the enteric nervous system and smooth muscle in the gut, may be involved in the gut-mediated glucose homeostasis [5,6] . Pharmacologic stimulation of serotonin 5-HT1B or 5-HT4 receptors increases plasma active glucagon-like-peptide-1 levels independently of feeding and improves glucose tolerance under the dipeptidyl peptidase-4 inhibition in mice [5,6] . Although it remains unclear whether gut microbiota influence insulin secretion, the gut microviota-5-HT axis may be a novel therapeutic target for type 2 diabetes in future. References 1. Qin, J., Li. Y., Cai, Z., et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. (2012) Nature 490(7418): 55-60. 2. Karlsson, F.H., Tremaroli, V., Nookaew, I., et al. Gut metagenome in European women with normal, impaired and diabetic glucose control. (2013) Nature 498(7942): 99-103. 3. Forslund, K., Hildebrand, F., Nielsen, T., et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. (2015) Nature. 4. Yano, J., Yu, K., Donaldson, G.P., et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. (2015) Cell 161(2): 264-276. 5. Nonogaki, K., Kaji, T. Pharmacological stimulation of serotonin 5-HT1B receptors enhances increases in plasma active glucagon-like peptide-1 levels induced by dipeptidyl peptidase-4 inhibition independently of feeding in mice. (2015) Diabetes Metab 41(5): 425-428. 6. Nonogaki, K., Kaji, T. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice. (2015) Diabetes Res Clin Pract.