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

Author

Listed:
  • Xinyang Song

    (Blavatnik Institute, Harvard Medical School)

  • Ximei Sun

    (Blavatnik Institute, Harvard Medical School)

  • Sungwhan F. Oh

    (Blavatnik Institute, Harvard Medical School
    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
    Technion–Israel Institute of Technology)

  • 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)

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.

Suggested Citation

  • Xinyang Song & Ximei Sun & Sungwhan F. Oh & Meng Wu & Yanbo Zhang & Wen Zheng & Naama Geva-Zatorsky & Ray Jupp & Diane Mathis & Christophe Benoist & Dennis L. Kasper, 2020. "Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis," Nature, Nature, vol. 577(7790), pages 410-415, January.
  • Handle: RePEc:nat:nature:v:577:y:2020:i:7790:d:10.1038_s41586-019-1865-0
    DOI: 10.1038/s41586-019-1865-0
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    Cited by:

    1. Xiaoxue Jiang & Kan liu & Peixiang Luo & Zi Li & Fei Xiao & Haizhou Jiang & Shangming Wu & Min Tang & Feixiang Yuan & Xiaoying Li & Yousheng Shu & Bo Peng & Shanghai Chen & Shihong Ni & Feifan Guo, 2024. "Hypothalamic SLC7A14 accounts for aging-reduced lipolysis in white adipose tissue of male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Xusheng Zhang & Xintong Gao & Zhen Liu & Fei Shao & Dou Yu & Min Zhao & Xiwen Qin & Shuo Wang, 2024. "Microbiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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