2025-03-17 スイス連邦工科大学ローザンヌ校(EPFL)
<関連情報>
- https://actu.epfl.ch/news/gut-bacteria-heal-the-colon/
- https://www.embopress.org/doi/full/10.1038/s44321-025-00202-w
胆汁酸7α-デヒドロキシル化細菌は大腸の傷害性粘膜治癒を促進する Bile acid 7α-dehydroxylating bacteria accelerate injury-induced mucosal healing in the colon
Antoine Jalil, Alessia Perino, Yuan Dong, Jéromine Imbach, Colin Volet, Eduard Vico-Oton, Hadrien Demagny, Lucie Plantade, Hector Gallart-Ayala, Julijana Ivanisevic, Rizlan Bernier-Latmani, Siegfried Hapfelmeier, and Kristina Schoonjans
EMBO Molecular Medicine Published:10 March 2025
DOI:https://doi.org/10.1038/s44321-025-00202-w
Abstract
Host-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7α-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7α-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7α-dehydroxylating bacterium, can reestablish intestinal epithelium homeostasis following colon injury. Gnotobiotic and conventional mice were subjected to chemically-induced experimental colitis following administration of Clostridium scindens. Colonization enhanced the production of 7α-dehydroxylated bile acids and conferred prophylactic and therapeutic protection against colon injury through epithelial regeneration and specification. Computational analysis of human datasets confirmed defects in intestinal cell renewal and differentiation in ulcerative colitis patients while expression of genes involved in those pathways showed a robust positive correlation with 7α-dehydroxylated bile acid levels. Clostridium scindens administration could therefore be a promising biotherapeutic strategy to foster mucosal healing following colon injury by restoring bile acid homeostasis.
Synopsis
Clostridium scindens acts as a promising biotherapeutic to restore bile acid (BA) homeostasis, which is altered in ulcerative colitis (UC) patients. Its 7α-dehydroxylated BA products alleviate disease severity by promoting intestinal regeneration and mucosal healing in a dextran sulfate sodium (DSS) colitis mouse model.
- 7α-dehydroxylated BAs act via the BA receptor TGR5.
- Clostridium scindens colonization protected Tgr5 wild-type, but not Tgr5 knock-out mice from chemically-induced epithelial injury.
- Administration of Clostridium scindens after colitis onset improved disease outcomes in DSS-induced colon injury.
- 7α-dehydroxylated BA levels strongly correlate with intestinal epithelial cell specification in UC patients.
- Mucosal healing is a promising alternative to inflammation-targeting therapies in UC.
