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

Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation.
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DOI:
10.1038/s41586-022-05380-y
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发表时间:
2022-11
期刊:
影响因子:
64.8
通讯作者:
Artis, David
Artis, David
中科院分区:
综合性期刊1区
文献类型:
--
作者:
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 Garbes;Tsou, Amy M.;Chu, Coco;Wei, Qianru;Grier, Alex;Worgall, Stefan;Guo, Chun-Jun;Schroeder, Frank C.;Artis, David

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膳食纤维可以通过微生物发酵的短链脂肪酸代谢物发挥有益的抗炎作用,尽管大多数纤维饮食及其微生物衍生代谢物的免疫调节作用仍不清楚。在这里,利用微生物测序和非靶向代谢组学,我们发现菊粉纤维饮食改变了小鼠微生物群的组成以及微生物群衍生的代谢物(尤其是胆汁酸)的水平。这种代谢组学的转变与肠道和肺部的 2 型炎症相关,其特征是 IL-33 的产生、第 2 组先天淋巴细胞的激活和嗜酸性粒细胞增多。胆酸的输送模拟了菊粉诱导的 2 型炎症,而胆汁酸受体法尼醇 X 受体的缺失会减弱菊粉的作用。菊粉的作用依赖于微生物群,并在人类来源的微生物群定植的小鼠中重现。此外,一种细菌物种中胆汁酸代谢酶的基因缺失会消除菊粉引发 2 型炎症的能力。最后,我们证明菊粉可增强过敏原和蠕虫引起的 2 型炎症。总而言之,这些数据表明膳食菊粉纤维会引发屏障表面微生物群衍生的胆酸和 2 型炎症,这对于了解过敏性炎症的病理生理学、组织保护和宿主防御具有重要意义。
Dietary fibres can exert beneficial anti-inflammatory effects through microbially fermented short-chain fatty acid metabolites, 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.
宿主代谢和免疫系统界面处的共生细菌。
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