腸内細菌が大腸を修復する仕組みを解明(Gut Bacteria Heal the Colon)

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2025-03-17 スイス連邦工科大学ローザンヌ校(EPFL)

スイス連邦工科大学ローザンヌ校(EPFL)の研究者たちは、腸内細菌が大腸の健康維持に重要な役割を果たすことを明らかにしました。彼らは、特定の腸内細菌が短鎖脂肪酸を生成し、これが大腸の上皮細胞の修復と再生を促進することを発見しました。この研究は、腸内フローラのバランスが崩れると、大腸の炎症性疾患や他の健康問題のリスクが高まる可能性があることを示唆しています。さらに、腸内細菌のバランスを回復させるための治療法、例えば糞便微生物移植(FMT)などが、大腸の健康を改善する潜在的な手段として注目されています。

<関連情報>

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

腸内細菌が大腸を修復する仕組みを解明(Gut Bacteria Heal the Colon)

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.
医療・健康
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