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© Benoît Chassaing
Interaction microbiote-mucus à la surface de l’épithélium colique humain
Publication : Nature metabolism

Commensal bacteria weaken the intestinal barrier by suppressing epithelial neuropilin-1 and Hedgehog signaling.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature metabolism - 01 Jul 2023

Pontarollo G, Kollar B, Mann A, Khuu MP, Kiouptsi K, Bayer F, Brandão I, Zinina VV, Hahlbrock J, Malinarich F, Mimmler M, Bhushan S, Marini F, Ruf W, Belheouane M, Baines JF, Endres K, Reba SM, Raker VK, Deppermann C, Welsch C, Bosmann M, Soshnikova N, Chassaing B, Bergentall M, Sommer F, Bäckhed F, Reinhardt C

Link to Pubmed [PMID] – 37414930

Link to DOI – 10.1038/s42255-023-00828-5

Nat Metab 2023 Jul; 5(7): 1174-1187

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 (Nrp1ΔIEC) results in decreased Hh pathway activity and a weakened gut barrier. In addition, Nrp1ΔIEC 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.