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 |
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Alternate Journal | Nature |
PubMed ID | 36323778 |
PubMed Central ID | 4013146 |
Grant List | / HHMI / Howard Hughes Medical Institute / United States T32 HL134629 / HL / NHLBI NIH HHS / United States R21 AI140724 / AI / NIAID NIH HHS / United States KL2 TR002385 / TR / NCATS NIH HHS / United States R35 GM131877 / GM / NIGMS NIH HHS / United States R01 DK126871 / DK / NIDDK NIH HHS / United States R01 AI151599 / AI / NIAID NIH HHS / United States R01 AI095466 / AI / NIAID NIH HHS / United States U01 AI095608 / AI / NIAID NIH HHS / United States R01 AR070116 / AR / NIAMS NIH HHS / United States R01 AI172027 / AI / NIAID NIH HHS / United States R01 DK132244 / DK / NIDDK NIH HHS / United States |