Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.

ABSTRACT: The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered w

SUBMITTER: Kellogg TD 

PROVIDER: S-EPMC11602550 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature