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

Mohammad Arifuzzaman, Tae Hyung Won, Ting-Ting Li, Hiroshi Yano, Sreehaas Digumarthi, Andrea F. Heras, Wen Zhang, Christopher N. Parkhurst, Sanchita Kashyap, Wen-Bing Jin, Gregory Garbès Putzel, Amy M. Tsou, Coco Chu, Qianru Wei, Alex Grier, Stefan Worgall, Chun-Jun Guo (), Frank C. Schroeder () and David Artis ()
Additional contact information
Mohammad Arifuzzaman: Weill Cornell Medicine, Cornell University
Tae Hyung Won: Cornell University
Ting-Ting Li: Weill Cornell Medicine, Cornell University
Hiroshi Yano: Weill Cornell Medicine, Cornell University
Sreehaas Digumarthi: Weill Cornell Medicine, Cornell University
Andrea F. Heras: Weill Cornell Medicine, Cornell University
Wen Zhang: Weill Cornell Medicine, Cornell University
Christopher N. Parkhurst: Weill Cornell Medicine, Cornell University
Sanchita Kashyap: Weill Cornell Medicine, Cornell University
Wen-Bing Jin: Weill Cornell Medicine, Cornell University
Gregory Garbès Putzel: Weill Cornell Medicine, Cornell University
Amy M. Tsou: Weill Cornell Medicine, Cornell University
Coco Chu: Weill Cornell Medicine, Cornell University
Qianru Wei: Weill Cornell Medicine, Cornell University
Alex Grier: Weill Cornell Medicine, Cornell University
Stefan Worgall: Weill Cornell Medicine, Cornell University
Chun-Jun Guo: Weill Cornell Medicine, Cornell University
Frank C. Schroeder: Cornell University
David Artis: Weill Cornell Medicine, Cornell University

Nature, 2022, vol. 611, issue 7936, 578-584

Abstract: Abstract Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites1,2, 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.

Date: 2022
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DOI: 10.1038/s41586-022-05380-y

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