| First Author | Li C | Year | 2024 |
| Journal | Cell Host Microbe | Volume | 32 |
| Issue | 6 | Pages | 950-963.e8 |
| PubMed ID | 38788722 | Mgi Jnum | J:352365 |
| Mgi Id | MGI:7658704 | Doi | 10.1016/j.chom.2024.04.020 |
| Citation | Li C, et al. (2024) Enterococcus-derived tyramine hijacks alpha(2A)-adrenergic receptor in intestinal stem cells to exacerbate colitis. Cell Host Microbe 32(6):950-963.e8 |
| abstractText | Inflammatory bowel disease (IBD) is characterized by dysbiosis of the gut microbiota and dysfunction of intestinal stem cells (ISCs). However, the direct interactions between IBD microbial factors and ISCs are undescribed. Here, we identify alpha(2A)-adrenergic receptor (ADRA2A) as a highly expressed GPCR in ISCs. Through PRESTO-Tango screening, we demonstrate that tyramine, primarily produced by Enterococcus via tyrosine decarboxylase (tyrDC), serves as a microbial ligand for ADRA2A. Using an engineered tyrDC-deficient Enterococcus faecalis strain and intestinal epithelial cell-specific Adra2a knockout mice, we show that Enterococcus-derived tyramine suppresses ISC proliferation, thereby impairing epithelial regeneration and exacerbating DSS-induced colitis through ADRA2A. Importantly, blocking the axis with an ADRA2A antagonist, yohimbine, disrupts tyramine-mediated suppression on ISCs and alleviates colitis. Our findings highlight a microbial ligand-GPCR pair in ISCs, revealing a causal link between microbial regulation of ISCs and colitis exacerbation and yielding a targeted therapeutic approach to restore ISC function in colitis. |
