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

被引：1271

作者：

Macia, Laurence ^{[1
]}

Tan, Jian ^{[1
]}

Vieira, Angelica T. ^{[1
,2
]}

Leach, Katie ^{[3
]}

Stanley, Dragana ^{[4
,5
]}

Luong, Suzanne ^{[1
]}

Maruya, Mikako ^{[6
,7
]}

McKenzie, Craig Ian ^{[1
]}

Hijikata, Atsushi ^{[6
,7
]}

Wong, Connie ^{[1
]}

Binge, Lauren ^{[1
]}

Thorburn, Alison N. ^{[1
]}

Chevalier, Nina ^{[1
]}

Ang, Caroline ^{[1
]}

Marino, Eliana ^{[1
]}

Robert, Remy ^{[1
]}

Offermanns, Stefan ^{[8
]}

Teixeira, Mauro M. ^{[2
]}

Moore, Robert J. ^{[4
,9
]}

Flavell, Richard A. ^{[10
,11
]}

Fagarasan, Sidonia ^{[6
,7
]}

Mackay, Charles R. ^{[1
]}

机构：

[1] Monash Univ, Fac Med Nursing & Hlth Sci, Dept Immunol, Clayton, Vic 3800, Australia

[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biochem & Immunol, Immunopharmacol Grp, BR-31270901 Belo Horizonte, MG, Brazil

[3] Monash Univ, Fac Pharm & Pharmaceut Sci, Parkville, Vic 3052, Australia

[4] CSIRO Anim Food & Hlth Sci, Australian Anim Hlth Labs, Geelong, Vic 3220, Australia

[5] Cent Queensland Univ, Sch Med & Appl Sci, Rockhampton, Qld 4702, Australia

[6] RIKEN, Res Ctr Allergy & Immunol, Lab Mucosal Immun, Yokohama, Kanagawa 2300045, Japan

[7] RIKEN, Res Ctr Allergy & Immunol, Lab Immunogenom, Yokohama, Kanagawa 2300045, Japan

[8] Max Planck Inst Heart & Lung Res, D-61231 Bad Nauheim, Germany

[9] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Clayton, Vic 3800, Australia

[10] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA

[11] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国医学研究理事会;

关键词：

CHAIN FATTY-ACIDS; NICOTINIC-ACID; NLRP3; INFLAMMASOME; COLONIC MICROBIOTA; HEALTH; ACTIVATION; BUTYRATE; IMPACT; IMMUNITY; OBESITY;

D O I：

10.1038/ncomms7734

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：15

共 48 条

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