Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome

Laurence Macia, Jian Tan, Angelica T. Vieira, Katie Leach, Dragana Stanley, Suzanne Luong, Mikako Maruya, Craig Ian McKenzie, Atsushi Hijikata, Connie Wong, Lauren Binge, Alison N. Thorburn, Nina Chevalier, Caroline Ang, Eliana Marino, Remy Robert, Stefan Offermanns, Mauro M. Teixeira, Robert J. Moore, Richard A. Flavell, Sidonia Fagarasan and Charles R. Mackay ()
Additional contact information
Laurence Macia: Faculty of Medicine, Nursing and Health Sciences, Monash University
Jian Tan: Faculty of Medicine, Nursing and Health Sciences, Monash University
Angelica T. Vieira: Faculty of Medicine, Nursing and Health Sciences, Monash University
Katie Leach: Faculty of Pharmacy and Pharmaceutical Sciences, Monash University
Dragana Stanley: CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories
Suzanne Luong: Faculty of Medicine, Nursing and Health Sciences, Monash University
Mikako Maruya: Laboratory for Mucosal Immunity, 6 Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology Tsurumi
Craig Ian McKenzie: Faculty of Medicine, Nursing and Health Sciences, Monash University
Atsushi Hijikata: Laboratory for Mucosal Immunity, 6 Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology Tsurumi
Connie Wong: Faculty of Medicine, Nursing and Health Sciences, Monash University
Lauren Binge: Faculty of Medicine, Nursing and Health Sciences, Monash University
Alison N. Thorburn: Faculty of Medicine, Nursing and Health Sciences, Monash University
Nina Chevalier: Faculty of Medicine, Nursing and Health Sciences, Monash University
Caroline Ang: Faculty of Medicine, Nursing and Health Sciences, Monash University
Eliana Marino: Faculty of Medicine, Nursing and Health Sciences, Monash University
Remy Robert: Faculty of Medicine, Nursing and Health Sciences, Monash University
Stefan Offermanns: Max-Planck-Institute for Heart and Lung Research
Mauro M. Teixeira: Immunopharmacology Group, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais
Robert J. Moore: CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories
Richard A. Flavell: Yale University School of Medicine
Sidonia Fagarasan: Laboratory for Mucosal Immunity, 6 Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology Tsurumi
Charles R. Mackay: Faculty of Medicine, Nursing and Health Sciences, Monash University

Nature Communications, 2015, vol. 6, issue 1, 1-15

Abstract: Abstract Diet and the gut microbiota may underpin numerous human diseases. A major metabolic product of commensal bacteria are short-chain fatty acids (SCFAs) that derive from fermentation of dietary fibre. Here we show that diets deficient or low in fibre exacerbate colitis development, while very high intake of dietary fibre or the SCFA acetate protects against colitis. SCFAs binding to the ‘metabolite-sensing’ receptors GPR43 and GPR109A in non-haematopoietic cells mediate these protective effects. The inflammasome pathway has hitherto been reported as a principal pathway promoting gut epithelial integrity. SCFAs binding to GPR43 on colonic epithelial cells stimulates K+ efflux and hyperpolarization, which lead to NLRP3 inflammasome activation. Dietary fibre also shapes gut bacterial ecology, resulting in bacterial species that are more effective for inflammasome activation. SCFAs and metabolite receptors thus explain health benefits of dietary fibre, and how metabolite signals feed through to a major pathway for gut homeostasis.

Date: 2015
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DOI: 10.1038/ncomms7734

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