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

• Published in: Nature (London) Vol. 611; no. 7936; pp. 578 - 584
• Main Authors: Arifuzzaman, Mohammad, Won, Tae Hyung, Li, Ting-Ting, Yano, Hiroshi, Digumarthi, Sreehaas, Heras, Andrea F., Zhang, Wen, Parkhurst, Christopher N., Kashyap, Sanchita, Jin, Wen-Bing, Putzel, Gregory Garbès, Tsou, Amy M., Chu, Coco, Wei, Qianru, Grier, Alex, Worgall, Stefan, Guo, Chun-Jun, Schroeder, Frank C., Artis, David
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.11.2022; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/31; 13/44; 14/63; 45/91; 631/250/2504/2506; 631/250/347; 631/326/2565/2134; 64/60; 82/58; Allergens; Animals; Bile; Bile acids; Bile Acids and Salts - metabolism; Cellulose; Cholic acid; Cholic Acid - pharmacology; Colon; Cytokines; Deletion; Dendritic cells; Diet; Dietary fiber; Dietary Fiber - pharmacology; Eosinophilia; Eosinophils - cytology; Eosinophils - drug effects; Eosinophils - immunology; Fatty acids; Fermented food; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Humanities and Social Sciences; Humans; Hypersensitivity; Immunity, Innate; Immunology; Immunoregulation; Inflammation; Inflammation - chemically induced; Inflammation - classification; Inflammation - pathology; Interleukin-33 - metabolism; Intestine; Intestines - drug effects; Intestines - microbiology; Intestines - pathology; Inulin; Inulin - pharmacology; Lung - drug effects; Lung - pathology; Lymphocytes; Lymphocytes - cytology; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphoid cells; Metabolism; Metabolites; Metabolomics; Mice; Microbiota; Microorganisms; multidisciplinary; Receptors; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-022-05380-y

Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites 1 , 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. Dietary inulin fibre alters the composition and metabolism of gut microbiota, resulting in elevated levels of bile acids that subsequently trigger mucosal type 2 inflammation characterized by eosinophilia, with clinical implications for allergy and anti-helminth defence.