Faecalibaculum rodentium remodels retinoic acid signaling to govern eosinophil-dependent intestinal epithelial homeostasis

Y. Grace Cao, Sena Bae, Jannely Villarreal, Madelyn Moy, Eunyoung Chun, Monia Michaud, Jessica K. Lang, Jonathan N. Glickman, Lior Lobel, Wendy S. Garrett

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The intestinal epithelium plays critical roles in sensing and integrating dietary and microbial signals. How microbiota and intestinal epithelial cell (IEC) interactions regulate host physiology in the proximal small intestine, particularly the duodenum, is unclear. Using single-cell RNA sequencing of duodenal IECs under germ-free (GF) and different conventional microbiota compositions, we show that specific microbiota members alter epithelial homeostasis by increasing epithelial turnover rate, crypt proliferation, and major histocompatibility complex class II (MHCII) expression. Microbiome profiling identified Faecalibaculum rodentium as a key species involved in this regulation. F. rodentium decreases enterocyte expression of retinoic-acid-producing enzymes Adh1, Aldh1a1, and Rdh7, reducing retinoic acid signaling required to maintain certain intestinal eosinophil populations. Eosinophils suppress intraepithelial-lymphocyte-mediated production of interferon-γ that regulates epithelial cell function. Thus, we identify a retinoic acid-eosinophil-interferon-γ-dependent circuit by which the microbiota modulates duodenal epithelial homeostasis.

Original languageEnglish
Pages (from-to)1295-1310.e8
JournalCell Host and Microbe
Volume30
Issue number9
DOIs
StatePublished - 14 Sep 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Faecalibaculum rodentium
  • duodenum
  • eosinophil
  • interferon-γ
  • intestinal epithelial cell
  • microbiota
  • retinoic acid
  • small intestine

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