Diabetes Metab J.  2015 Jun;39(3):198-203. 10.4093/dmj.2015.39.3.198.

Gut Microbiota and Metabolic Disorders

• Hur KY
• Lee MS

• KMID: 2281532
• DOI: http://doi.org/10.4093/dmj.2015.39.3.198

Abstract

Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

Keyword

Gut; Metformin; Microbiota; Obesity

MeSH Terms

Eating
Fatty Acids, Volatile
Gastrointestinal Diseases
Hypoglycemic Agents
Insulin
Metabolism
Metformin
Microbiota*
Obesity
Prebiotics
Probiotics
Fatty Acids, Volatile
Hypoglycemic Agents
Insulin
Metformin
Prebiotics

Figure

• 

  Fig. 1 Gut microbiota regulation of host metabolism. Undigested carbohydrates are fermented by gut microbiota into short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate. SCFAs affect the host metabolism in several ways. SCFAs can signal through G protein-coupled receptor 41 (GPR41) on enteroendocrine cells, inducing the secretion of peptide YY (PYY) which inhibits gut motility, increases intestinal transit rate, and reduces the harvest of energy from the diet. Engagement of GPR43 by SCFAs has been shown to trigger the glucogon-like peptide 1 (GLP-1) to increase insulin sensitivity. Gut microbiota efficiently suppresses fasting-induced adipose factor (Fiaf) expression in the ileum, which inhibits lipoprotein lipase (LPL) activity and fat storage in white adipose tissue. SCFAs-mediated activation of GPR43 results in suppression of insulin signaling in the adipose tissue and subsequent prevention of fat accumulation. SCFAs also activate intestinal gluconeogenesis (IGN) via a gut-brain neural circuit, which can improve glucose metabolism and reduce food intake. VLDL, very low density lipoprotein; FFA, free fatty acid.

• 

  Fig. 2 Effect of high fat diet (HFD) and metformin on gut microbiota and intestinal environment. A HFD induces gut microbial alteration, which increases gut permeability and reduces the expression of tight junction protein, such as zonula occludens (ZO)-1 and occludin, in the intestinal epithelial cells, results in the passage of lipopolysaccharide (LPS) into the portal blood circulation. The disruption of the gut barrier function and the gut microbiota-derived endotoxemia could contribute to the pathogenesis of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). Metformin is able to affect the mouse microbiota and restored the decreased abundance of Akkermansia muciniphila, a mucin-degrading G (-) anaerobes, in the gut of mice fed a HFD to that of mice fed normal chow diet. A. muciniphila had similar beneficial metabolic effects to that of metformin administration.

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