Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis

Xinyang Song, Ximei Sun, Sungwhan F. Oh, Meng Wu, Yanbo Zhang, Wen Zheng, Naama Geva-Zatorsky, Ray Jupp, Diane Mathis, Christophe Benoist and Dennis L. Kasper ()
Additional contact information
Xinyang Song: Blavatnik Institute, Harvard Medical School
Ximei Sun: Blavatnik Institute, Harvard Medical School
Sungwhan F. Oh: Blavatnik Institute, Harvard Medical School
Meng Wu: Blavatnik Institute, Harvard Medical School
Yanbo Zhang: Blavatnik Institute, Harvard Medical School
Wen Zheng: Blavatnik Institute, Harvard Medical School
Naama Geva-Zatorsky: Blavatnik Institute, Harvard Medical School
Ray Jupp: UCB Pharma
Diane Mathis: Blavatnik Institute, Harvard Medical School
Christophe Benoist: Blavatnik Institute, Harvard Medical School
Dennis L. Kasper: Blavatnik Institute, Harvard Medical School

Nature, 2020, vol. 577, issue 7790, 410-415

Abstract: Abstract The metabolic pathways encoded by the human gut microbiome constantly interact with host gene products through numerous bioactive molecules1. Primary bile acids (BAs) are synthesized within hepatocytes and released into the duodenum to facilitate absorption of lipids or fat-soluble vitamins2. Some BAs (approximately 5%) escape into the colon, where gut commensal bacteria convert them into various intestinal BAs2 that are important hormones that regulate host cholesterol metabolism and energy balance via several nuclear receptors and/or G-protein-coupled receptors3,4. These receptors have pivotal roles in shaping host innate immune responses1,5. However, the effect of this host–microorganism biliary network on the adaptive immune system remains poorly characterized. Here we report that both dietary and microbial factors influence the composition of the gut BA pool and modulate an important population of colonic FOXP3+ regulatory T (Treg) cells expressing the transcription factor RORγ. Genetic abolition of BA metabolic pathways in individual gut symbionts significantly decreases this Treg cell population. Restoration of the intestinal BA pool increases colonic RORγ+ Treg cell counts and ameliorates host susceptibility to inflammatory colitis via BA nuclear receptors. Thus, a pan-genomic biliary network interaction between hosts and their bacterial symbionts can control host immunological homeostasis via the resulting metabolites.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1865-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:577:y:2020:i:7790:d:10.1038_s41586-019-1865-0

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-1865-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().