| First Author | Zhao Y | Year | 2018 |
| Journal | Mucosal Immunol | Volume | 11 |
| Issue | 3 | Pages | 752-762 |
| PubMed ID | 29411774 | Mgi Jnum | J:275563 |
| Mgi Id | MGI:6305606 | Doi | 10.1038/mi.2017.118 |
| Citation | Zhao Y, et al. (2018) GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol 11(3):752-762 |
| abstractText | The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIIIgamma and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIIIgamma and beta-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43(-/-) mice compared to that of wild-type (WT) mice. Oral feeding with short-chain fatty acids (SCFA) promoted IEC production of RegIIIgamma and defensins in mice. Furthermore, SCFA induced RegIIIgamma and beta-defensins in intestinal epithelial enteroids generated from WT but not GPR43(-/-) mice. Mechanistically, SCFA activated mTOR and STAT3 in IEC, and knockdown of mTOR and STAT3 impaired SCFA induction of AMP production. Our studies thus demonstrated that microbiota metabolites SCFA promoted IEC RegIIIgamma and beta-defensins in a GPR43-dependent manner. The data thereby provide a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis. |
