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 language | English |
|---|---|
| Pages (from-to) | 1295-1310.e8 |
| Journal | Cell Host and Microbe |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| State | Published - 14 Sep 2022 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2022 Elsevier Inc.
Funding
This work is supported by NIH grant R24 DK110499 to W.S.G. and NIH T32 AI118692, F31 DK121375, and the Karen Doreen Keim Scholarship to Y.G.C. We thank L. Ricci for preparing the graphical abstract. We thank the Garrett Laboratory and Dr. A. Pawluk for helpful discussions and manuscript review. Conceptualization, Y.G.C. and W.S.G.; formal analysis, Y.G.C. and S.B.; funding acquisition, Y.G.C. and W.S.G.; investigation, Y.G.C. J.V. M. Moy, E.C. M. Michaud, J.K.L. J.N.G. and L.L.; supervision, W.S.G.; visualization, Y.G.C. and W.S.G.; writing – original draft, Y.G.C. and W.S.G.; writing – review and editing, all authors. W.S.G. is on the SAB of Senda Biosciences, Freya Biosciences, and Artizan Biosciences, all outside the current work. This work is supported by NIH grant R24 DK110499 to W.S.G. and NIH T32 AI118692 , F31 DK121375 , and the Karen Doreen Keim Scholarship to Y.G.C. We thank L. Ricci for preparing the graphical abstract. We thank the Garrett Laboratory and Dr. A. Pawluk for helpful discussions and manuscript review.
| Funders | Funder number |
|---|---|
| Karen Doreen Keim Scholarship | |
| National Institutes of Health | F31 DK121375, R24 DK110499 |
| National Institute of Allergy and Infectious Diseases | T32AI118692 |
| Sächsische Aufbaubank |
Keywords
- Faecalibaculum rodentium
- duodenum
- eosinophil
- interferon-γ
- intestinal epithelial cell
- microbiota
- retinoic acid
- small intestine