Title | Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Arifuzzaman, M, Won, THyung, Li, T-T, Yano, H, Digumarthi, S, Heras, AF, Zhang, W, Parkhurst, CN, Kashyap, S, Jin, W-B, Putzel, GGarbès, Tsou, AM, Chu, C, Wei, Q, Grier, A, Worgall, S, Guo, C-J, Schroeder, FC, Artis, D |
Corporate Authors | JRI IBD Live Cell Bank Consortium |
Journal | Nature |
Volume | 611 |
Issue | 7936 |
Pagination | 578-584 |
Date Published | 2022 Nov |
ISSN | 1476-4687 |
Keywords | Animals, Bile Acids and Salts, Cholic Acid, Dietary Fiber, Eosinophils, Gastrointestinal Microbiome, Humans, Immunity, Innate, Inflammation, Interleukin-33, Intestines, Inulin, Lung, Lymphocytes, Metabolomics, Mice |
Abstract | Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites<sup>1,2</sup>, although the immunoregulatory roles of most fibre diets and their microbiota-derived metabolites remain poorly defined. Here, using microbial sequencing and untargeted metabolomics, we show that a diet of inulin fibre alters the composition of the mouse microbiota and the levels of microbiota-derived metabolites, notably bile acids. This metabolomic shift is associated with type 2 inflammation in the intestine and lungs, characterized by IL-33 production, activation of group 2 innate lymphoid cells and eosinophilia. Delivery of cholic acid mimics inulin-induced type 2 inflammation, whereas deletion of the bile acid receptor farnesoid X receptor diminishes the effects of inulin. The effects of inulin are microbiota dependent and were reproduced in mice colonized with human-derived microbiota. Furthermore, genetic deletion of a bile-acid-metabolizing enzyme in one bacterial species abolishes the ability of inulin to trigger type 2 inflammation. Finally, we demonstrate that inulin enhances allergen- and helminth-induced type 2 inflammation. Taken together, these data reveal that dietary inulin fibre triggers microbiota-derived cholic acid and type 2 inflammation at barrier surfaces with implications for understanding the pathophysiology of allergic inflammation, tissue protection and host defence. |
DOI | 10.1038/s41586-022-05380-y |
Alternate Journal | Nature |
PubMed ID | 36323778 |
PubMed Central ID | PMC10576985 |
Grant List | DP2 HD101401 / HD / NICHD NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States R01 DK132244 / DK / NIDDK NIH HHS / United States R01 AI172027 / AI / NIAID NIH HHS / United States R35 GM131877 / GM / NIGMS NIH HHS / United States |