Gut microbial metabolites in obesity, NAFLD and T2DM

• Published in: Nature reviews. Endocrinology 2019-05, Vol.15 (5), p.261-273
• Main Authors: Canfora, Emanuel E., Meex, Ruth C. R., Venema, Koen, Blaak, Ellen E.
• Format: Article
• Language: English
• Subjects: 631/443/319; 692/698/2741/2135; 692/699/2743/137/773; 692/699/2743/393; Adipose tissue; Ammonia; Animals; Appetite; Carbohydrates; Colon; Colon - metabolism; Colon - microbiology; Complications and side effects; Development and progression; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - microbiology; Dietary fiber; Disease resistance; Endocrinology; Energy expenditure; Fatty acids; Fatty liver; Fermentation; Gastrointestinal Microbiome - physiology; Health aspects; Homeostasis; Humans; Insulin; Insulin resistance; Insulin Resistance - physiology; Intestinal microflora; Liver diseases; Medicine; Medicine & Public Health; Metabolic disorders; Metabolism; Metabolites; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - microbiology; Obesity; Obesity - metabolism; Obesity - microbiology; Phenols; Physiological aspects; Prevention; Proteins; Proteolysis; Review Article; Type 2 diabetes
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/s41574-019-0156-z

Evidence is accumulating that the gut microbiome is involved in the aetiology of obesity and obesity-related complications such as nonalcoholic fatty liver disease (NAFLD), insulin resistance and type 2 diabetes mellitus (T2DM). The gut microbiota is able to ferment indigestible carbohydrates (for example, dietary fibre), thereby yielding important metabolites such as short-chain fatty acids and succinate. Numerous animal studies and a handful of human studies suggest a beneficial role of these metabolites in the prevention and treatment of obesity and its comorbidities. Interestingly, the more distal colonic microbiota primarily ferments peptides and proteins, as availability of fermentable fibre, the major energy source for the microbiota, is limited here. This proteolytic fermentation yields mainly harmful products such as ammonia, phenols and branched-chain fatty acids, which might be detrimental for host gut and metabolic health. Therefore, a switch from proteolytic to saccharolytic fermentation could be of major interest for the prevention and/or treatment of metabolic diseases. This Review focuses on the role of products derived from microbial carbohydrate and protein fermentation in relation to obesity and obesity-associated insulin resistance, T2DM and NAFLD, and discusses the mechanisms involved. In this Review, the authors explore the role of gut microbial metabolites derived from carbohydrate fermentation and protein fermentation in body weight control, nonalcoholic fatty liver disease, insulin resistance and type 2 diabetes mellitus. Key points Gut microbial metabolites such as short-chain fatty acids (SCFAs) and succinate, which are derived from the fermentation of dietary fibre, have important metabolic functions. SCFAs and succinate might prevent obesity by increasing energy expenditure, increasing anorexic hormone production and improving appetite regulation. SCFAs have a crucial role in gut homeostasis, adipose tissue and liver substrate metabolism and function, through which they can prevent the progression of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). The site of microbial SCFA production in the colon might be an important determinant for the aforementioned beneficial effects. The microbial metabolites derived from protein fermentation, which are mainly produced in the distal colon, are most often considered detrimental for gut integrity and metabolic health. Providing mixtures of dietary fibres to inc