| First Author | Lei C | Year | 2022 |
| Journal | Cell Host Microbe | Volume | 30 |
| Issue | 10 | Pages | 1417-1434.e8 |
| PubMed ID | 36150396 | Mgi Jnum | J:347570 |
| Mgi Id | MGI:7366836 | Doi | 10.1016/j.chom.2022.09.001 |
| Citation | Lei C, et al. (2022) Enteric VIP-producing neurons maintain gut microbiota homeostasis through regulating epithelium fucosylation. Cell Host Microbe 30(10):1417-1434.e8 |
| abstractText | Interactions between the enteric nervous system (ENS) and intestinal epithelium are thought to play a vital role in intestinal homeostasis. How the ENS monitors the frontier with commensal and pathogenic microbes while maintaining epithelial function remains unclear. Here, by combining subdiaphragmatic vagotomy with transcriptomics, chemogenetic strategy, and coculture of enteric neuron-intestinal organoid, we show that enteric neurons expressing VIP shape the alpha1,2-fucosylation of intestinal epithelial cells (IECs). Mechanistically, neuropeptide VIP activates fut2 expression via the Erk1/2-c-Fos pathway through the VIPR1 receptor on IECs. We further demonstrate that perturbation of enteric neurons leads to gut dysbiosis through alpha1,2-fucosylation in the steady state and results in increased susceptibility to alcohol-associated liver disease (ALD). This was attributed to an imbalance between beneficial Bifidobacterium and opportunistic pathogenic Enterococcus faecalis in ALD. In addition, Bifidobacterium alpha1,2-fucosidase may promote Bifidobacterium adhesion to the mucosal surface, which restricts Enterococcus faecalis overgrowth and prevents ALD progression. |
