Inulin fibre promotes microbiota-derived bile acids and type 2 inflammation.
Animals
Humans
Mice
Bile Acids and Salts
/ metabolism
Cholic Acid
/ pharmacology
Dietary Fiber
/ pharmacology
Gastrointestinal Microbiome
/ drug effects
Immunity, Innate
Inflammation
/ chemically induced
Inulin
/ pharmacology
Lymphocytes
/ cytology
Metabolomics
Lung
/ drug effects
Intestines
/ drug effects
Interleukin-33
/ metabolism
Eosinophils
/ cytology
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
received:
10
01
2021
accepted:
22
09
2022
pubmed:
4
11
2022
medline:
22
11
2022
entrez:
3
11
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36323778
doi: 10.1038/s41586-022-05380-y
pii: 10.1038/s41586-022-05380-y
pmc: PMC10576985
mid: NIHMS1934455
doi:
Substances chimiques
Bile Acids and Salts
0
Cholic Acid
G1JO7801AE
Dietary Fiber
0
Inulin
9005-80-5
farnesoid X-activated receptor
0C5V0MRU6P
Interleukin-33
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
578-584Subventions
Organisme : NICHD NIH HHS
ID : DP2 HD101401
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK132244
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI172027
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM131877
Pays : United States
Investigateurs
Randy Longman
(R)
Gregory Sonnenberg
(G)
Ellen Scherl
(E)
Robbyn Sockolow
(R)
Dana Lukin
(D)
Robert Battat
(R)
Thomas Ciecierega
(T)
Aliza Solomon
(A)
Elaine Barfield
(E)
Kimberley Chien
(K)
Johanna Ferreira
(J)
Jasmin Williams
(J)
Shaira Khan
(S)
Peik Sean Chong
(PS)
Samah Mozumder
(S)
Lance Chou
(L)
Wenqing Zhou
(W)
Anees Ahmed
(A)
Connie Zhong
(C)
Ann Joseph
(A)
Joseph Gladstone
(J)
Samantha Jensen
(S)
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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