Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation.

TitleInulin fibre promotes microbiota-derived bile acids and type 2 inflammation.
Publication TypeJournal Article
Year of Publication2022
AuthorsArifuzzaman, 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 AuthorsJRI IBD Live Cell Bank Consortium
JournalNature
Volume611
Issue7936
Pagination578-584
Date Published2022 Nov
ISSN1476-4687
KeywordsAnimals, 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.

DOI10.1038/s41586-022-05380-y
Alternate JournalNature
PubMed ID36323778
PubMed Central IDPMC10576985
Grant ListDP2 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