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 McKenzie, Atsushi Hijikata, Connie H Y Wong, Lauren Clare Binge, Alison N Thorburn, Nina Chevalier, Caroline Ang Kim Lian, Eliana Marino Moreno, Remy Robert, Stefan Offermanns, Mauro M Teixeira, Robert J Moore, Richard A Flavell & 2 others Sidonia Fagarasan, Charles R Mackay

Research output: Contribution to journalArticleResearchpeer-review

292 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1 - 15
Number of pages15
JournalNature Communications
Volume6
Issue number(Art. No: 7734)
DOIs
Publication statusPublished - 2015

Cite this

Macia, Laurence ; Tan, Jian ; Vieira, Angelica T ; Leach, Katie ; Stanley, Dragana ; Luong, Suzanne ; Maruya, Mikako ; McKenzie, Craig ; Hijikata, Atsushi ; Wong, Connie H Y ; Binge, Lauren Clare ; Thorburn, Alison N ; Chevalier, Nina ; Ang Kim Lian, Caroline ; Marino Moreno, Eliana ; Robert, Remy ; Offermanns, Stefan ; Teixeira, Mauro M ; Moore, Robert J ; Flavell, Richard A ; Fagarasan, Sidonia ; Mackay, Charles R. / Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. In: Nature Communications. 2015 ; Vol. 6, No. (Art. No: 7734). pp. 1 - 15.
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title = "Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome",
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.",
author = "Laurence Macia and Jian Tan and Vieira, {Angelica T} and Katie Leach and Dragana Stanley and Suzanne Luong and Mikako Maruya and Craig McKenzie and Atsushi Hijikata and Wong, {Connie H Y} and Binge, {Lauren Clare} and Thorburn, {Alison N} and Nina Chevalier and {Ang Kim Lian}, Caroline and {Marino Moreno}, Eliana and Remy Robert and Stefan Offermanns and Teixeira, {Mauro M} and Moore, {Robert J} and Flavell, {Richard A} and Sidonia Fagarasan and Mackay, {Charles R}",
year = "2015",
doi = "10.1038/ncomms7734",
language = "English",
volume = "6",
pages = "1 -- 15",
journal = "Nature Communications",
issn = "2041-1723",
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Macia, L, Tan, J, Vieira, AT, Leach, K, Stanley, D, Luong, S, Maruya, M, McKenzie, C, Hijikata, A, Wong, CHY, Binge, LC, Thorburn, AN, Chevalier, N, Ang Kim Lian, C, Marino Moreno, E, Robert, R, Offermanns, S, Teixeira, MM, Moore, RJ, Flavell, RA, Fagarasan, S & Mackay, CR 2015, 'Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome', Nature Communications, vol. 6, no. (Art. No: 7734), pp. 1 - 15. https://doi.org/10.1038/ncomms7734

Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. / Macia, Laurence; Tan, Jian; Vieira, Angelica T; Leach, Katie; Stanley, Dragana; Luong, Suzanne; Maruya, Mikako; McKenzie, Craig; Hijikata, Atsushi; Wong, Connie H Y; Binge, Lauren Clare; Thorburn, Alison N; Chevalier, Nina; Ang Kim Lian, Caroline; Marino Moreno, Eliana; Robert, Remy; Offermanns, Stefan; Teixeira, Mauro M; Moore, Robert J; Flavell, Richard A; Fagarasan, Sidonia; Mackay, Charles R.

In: Nature Communications, Vol. 6, No. (Art. No: 7734), 2015, p. 1 - 15.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome

AU - Macia, Laurence

AU - Tan, Jian

AU - Vieira, Angelica T

AU - Leach, Katie

AU - Stanley, Dragana

AU - Luong, Suzanne

AU - Maruya, Mikako

AU - McKenzie, Craig

AU - Hijikata, Atsushi

AU - Wong, Connie H Y

AU - Binge, Lauren Clare

AU - Thorburn, Alison N

AU - Chevalier, Nina

AU - Ang Kim Lian, Caroline

AU - Marino Moreno, Eliana

AU - Robert, Remy

AU - Offermanns, Stefan

AU - Teixeira, Mauro M

AU - Moore, Robert J

AU - Flavell, Richard A

AU - Fagarasan, Sidonia

AU - Mackay, Charles R

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

UR - http://www.nature.com/ncomms/2015/150401/ncomms7734/pdf/ncomms7734.pdf

U2 - 10.1038/ncomms7734

DO - 10.1038/ncomms7734

M3 - Article

VL - 6

SP - 1

EP - 15

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - (Art. No: 7734)

ER -