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  • Review Article
  • Published:

Gut microbial metabolites in obesity, NAFLD and T2DM

Nature Reviews Endocrinology volume 15, pages 261–273 (2019)Cite this article

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Abstract

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.

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 increase distal colonic microbial carbohydrate fermentation and thereby inhibit protein fermentation might be a putative target to ameliorate obesity, T2DM and NAFLD.

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Fig. 1: Microbial communities and microbiological networks involved in saccharolytic and proteolytic metabolite production.
Fig. 2: Metabolites derived from carbohydrate fermentation in relation to body weight control.
Fig. 3: The relationship of metabolites derived from protein and carbohydrate fermentation and interorgan crosstalk with insulin resistance and type 2 diabetes mellitus.

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PubMed and Google Scholar were searched for relevant topics, using the search terms “SCFA”, “acetate”, “butyrate”, “propionate”, “succinate”, “dietary fibre”, probiotics”, “BCFA”, “ethanol”, “indoles”,”amines”, “sulfate”, “choline”, “bile acids” and “proteolytic fermentation” in combination with “intestinal concentrations”, “blood concentrations”, “microbiota”, “fermentation”, “intestinal homeostasis”, “obesity”, “NASH”, NAFLD”, “weight”, “satiety”, “type 2 diabetes”, “insulin sensitivity”, “insulin resistance”, “glycaemic control”, “glucose-lowering mechanisms”, “energy metabolism”, “inflammation”, “treg”, “vagal activity”, “cardiovascular disease” and “metabolic control”, without publication time constraints. References cited in this article include English-language original research and in some specific case reviews by experts in the field.

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Nature Reviews Endocrinology thanks G. Frost and other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, Netherlands

    Emanuel E. Canfora, Ruth C. R. Meex, Koen Venema & Ellen E. Blaak

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All authors provided a substantial contribution to the discussion of content; E.E.C. researched data for the article and wrote the article; and R.C.R.M., K.V. and E.E.B. reviewed and edited the manuscript before submission.

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Correspondence to Ellen E. Blaak.

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Canfora, E.E., Meex, R.C.R., Venema, K. et al. Gut microbial metabolites in obesity, NAFLD and T2DM. Nat Rev Endocrinol 15, 261–273 (2019). https://doi.org/10.1038/s41574-019-0156-z

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