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

doi:10.1038/ncomms7734

. 2015 Apr 1:6:6734.

doi: 10.1038/ncomms7734.

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

Laurence Macia¹, Jian Tan¹, Angelica T Vieira², Katie Leach³, Dragana Stanley⁴, Suzanne Luong¹, Mikako Maruya⁵, Craig Ian McKenzie¹, Atsushi Hijikata⁵, Connie Wong¹, Lauren Binge¹, Alison N Thorburn¹, Nina Chevalier¹, Caroline Ang¹, Eliana Marino¹, Remy Robert¹, Stefan Offermanns⁶, Mauro M Teixeira⁷, Robert J Moore⁸, Richard A Flavell⁹, Sidonia Fagarasan⁵, Charles R Mackay¹

Affiliations

¹ Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
² 1] Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia [2] Department of Biochemistry and Immunology, Immunopharmacology Group, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
³ Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
⁴ 1] CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories, Private Bag 24, Geelong, Victoria 3220, Australia [2] Central Queensland University, School of Medical and Applied Sciences, Bruce Highway, Rockhampton, Queensland 4702, Australia.
⁵ Laboratory for Mucosal Immunity, 6 Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology Tsurumi, Yokohama 230-0045, Japan.
⁶ Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
⁷ Department of Biochemistry and Immunology, Immunopharmacology Group, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
⁸ 1] CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories, Private Bag 24, Geelong, Victoria 3220, Australia [2] ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia.
⁹ 1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

PMID: 25828455
DOI: 10.1038/ncomms7734

Free article

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

Laurence Macia et al. Nat Commun. 2015.

Free article

. 2015 Apr 1:6:6734.

doi: 10.1038/ncomms7734.

Authors

Affiliations

¹ Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
² 1] Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Wellington Road, Clayton, Victoria 3800, Australia [2] Department of Biochemistry and Immunology, Immunopharmacology Group, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
³ Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
⁴ 1] CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories, Private Bag 24, Geelong, Victoria 3220, Australia [2] Central Queensland University, School of Medical and Applied Sciences, Bruce Highway, Rockhampton, Queensland 4702, Australia.
⁵ Laboratory for Mucosal Immunity, 6 Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology Tsurumi, Yokohama 230-0045, Japan.
⁶ Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231 Bad Nauheim, Germany.
⁷ Department of Biochemistry and Immunology, Immunopharmacology Group, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
⁸ 1] CSIRO Animal, Food and Health Sciences, Australian Animal Health Laboratories, Private Bag 24, Geelong, Victoria 3220, Australia [2] ARC Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Clayton, Victoria 3800, Australia.
⁹ 1] Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

PMID: 25828455
DOI: 10.1038/ncomms7734

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.

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

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

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