Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Dietary fibre induces gut homeostasis through metabolite-sensing GPCRs and regulation of the inflammasome pathway (#198)

Laurence Macia 1
  1. Monash University, Clayton, VIC, Australia

Human disease is affected by diet, as well as by the composition of the gut microbiota, through poorly understood mechanisms. One of the major activities of commensal microbes is digestion of dietary fibre, to yield short chain fatty acids (SCFAs). Deficiency of dietary fibre, in particular, has been associated with increased mortality due to various diseases, and decreasing amounts of fibre intake in western countries is one hypothesis for the increased incidences of certain inflammatory diseases. SCFAs affect numerous biological systems, either through stimulation of ‘metabolite-sensing’ G-protein coupled receptors such as GPR43, GPR41, and GPR109A or through inhibition of histone deacetylases. Here we show that diets deficient in fibre produced marked alterations in the composition of the gut microbiota in mice, and led to exacerbated disease in models of intestinal injury and inflammation, colon cancer, and wound healing. In contrast, very high intake of dietary fibre protected against these conditions. SCFAs binding to GPR43 and/or GPR109A were responsible for the protective effects of dietary fibre, in part through regulation of the NLRP3 inflammasome pathway. Simple conversion of mice to a high fibre diet yielded high levels in the blood and colon of the inflammasome related cytokine IL-18, which promotes gut epithelial integrity. Metabolites such as SCFAs and their receptors provide a link between the health benefits of dietary fibre, and other pathways important for gut homeostasis such as the inflammasome.