Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation.
Mohammad ArifuzzamanTae Hyung WonTing-Ting LiHiroshi YanoSreehaas DigumarthiAndrea F HerasWen ZhangChristopher N ParkhurstSanchita KashyapWen-Bing JinGregory Garbès PutzelAmy M TsouCoco ChuQianru WeiAlex Griernull nullStefan WorgallChun-Jun GuoFrank C SchroederDavid ArtisPublished in: Nature (2022)
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.
Keyphrases
- oxidative stress
- diabetic rats
- induced apoptosis
- fatty acid
- ms ms
- endothelial cells
- physical activity
- staphylococcus aureus
- electronic health record
- single cell
- microbial community
- weight loss
- adipose tissue
- cystic fibrosis
- pseudomonas aeruginosa
- endoplasmic reticulum stress
- drug induced
- candida albicans
- induced pluripotent stem cells
- deep learning
- genetic diversity
- simultaneous determination