AI Article Synopsis
- - The gut microbiota affects the integrity of the intestinal barrier, and this influence happens partly by inhibiting specific signaling pathways, namely the neuropilin-1 (NRP1) and Hedgehog (Hh) pathways.
- - Microbial colonization in germ-free mice reduces Hh pathway activity via Toll-like receptor (TLR)-2, leading to lower levels of NRP1, which is essential for maintaining the gut barrier.
- - Mice lacking NRP1 show decreased Hh signaling and weaker gut barriers, highlighting the importance of NRP1 and microbiota in gut health and structure.
Article Abstract
The gut microbiota influences intestinal barrier integrity through mechanisms that are incompletely understood. Here we show that the commensal microbiota weakens the intestinal barrier by suppressing epithelial neuropilin-1 (NRP1) and Hedgehog (Hh) signaling. Microbial colonization of germ-free mice dampens signaling of the intestinal Hh pathway through epithelial Toll-like receptor (TLR)-2, resulting in decreased epithelial NRP1 protein levels. Following activation via TLR2/TLR6, epithelial NRP1, a positive-feedback regulator of Hh signaling, is lysosomally degraded. Conversely, elevated epithelial NRP1 levels in germ-free mice are associated with a strengthened gut barrier. Functionally, intestinal epithelial cell-specific Nrp1 deficiency (Nrp1) results in decreased Hh pathway activity and a weakened gut barrier. In addition, Nrp1 mice have a reduced density of capillary networks in their small intestinal villus structures. Collectively, our results reveal a role for the commensal microbiota and epithelial NRP1 signaling in the regulation of intestinal barrier function through postnatal control of Hh signaling.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365997 | PMC |
| http://dx.doi.org/10.1038/s42255-023-00828-5 | DOI Listing |
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