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Butyrate generated by gut microbiota and its therapeutic role in metabolic syndrome

Bridgeman, SC, Northrop, W, Melton, PE ORCID: 0000-0003-4026-2964, Ellison, GC, Newsholme, P and Mamotte, CDS 2020 , 'Butyrate generated by gut microbiota and its therapeutic role in metabolic syndrome' , Pharmacological Research, vol. 160 , pp. 1-10 , doi: 10.1016/j.phrs.2020.105174.

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Metabolic syndrome (MetS) and the associated incidence of cardiovascular disease and type 2 diabetes represents a significant contributor to morbidity and mortality worldwide. Butyrate, a short-chain fatty acid produced by the gut microbiome, has long been known to promote growth in farmed animals and more recently has been reported to improve body weight and composition, lipid profile, insulin sensitivity and glycaemia in animal models of MetS. In vitro studies have examined the influence of butyrate on intestinal cells, adipose tissue, skeletal muscle, hepatocytes, pancreatic islets and blood vessels, highlighting genes and pathways that may contribute to its beneficial effects. Butyrate's influences in these cells have been attributed primarily to its epigenetic effects as a histone deacetylase inhibitor, as well as its role as an agonist of free fatty acid receptors, but clear mechanistic evidence is lacking. There is also uncertainty whether results from animal studies can translate to human trials due to butyrate's poor systemic availability and rapid clearance. Hitherto, several small-scale human clinical trials have failed to show significant benefits in MetS patients. Further trials are clearly needed, including with formulations designed to improve butyrate's availability. Regardless, dietary intervention to increase the rate of butyrate production may be a beneficial addition to current treatment. This review outlines the current body of evidence on the suitability of butyrate supplementation for MetS, looking at mechanistic effects on the various components of MetS and highlighting gaps in the knowledge and roadblocks to its use in humans.

Item Type: Article
Authors/Creators:Bridgeman, SC and Northrop, W and Melton, PE and Ellison, GC and Newsholme, P and Mamotte, CDS
Keywords: butyrate, diabetes, HDAC inhibitor, metabolic syndrome, short-chain fatty acid
Journal or Publication Title: Pharmacological Research
Publisher: Academic Press Ltd Elsevier Science Ltd
ISSN: 1043-6618
DOI / ID Number: 10.1016/j.phrs.2020.105174
Copyright Information:

Copyright 2020 Elsevier Ltd.

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