ArticleThe Journal of experimental medicine2025
Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.
Article in The Journal of experimental medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- 15-strain live biotherapeutic product or same donor fecal microbiota transplant for recurrent Clostridioides difficile infection: a randomized phase 1b trial.Nature medicine · 2026Trial
- The Nexus of Gut Microbiome, Microbial Metabolites, and Colonization Resistance Against Enteric Pathogens.Biomolecules · 2026Review
- Balancing act of cytokines in controlling the severity ofInfection and immunity · 2026Review
- Gastrointestinal tuft cells: Recent insights and next questions.Science immunology · 2026Review
- Review
- Article
- Metagenomic Insights into the Modulatory Effects of Thiamine Supplementation for Treating Subclinical Ketosis Dairy Cows.Animals : an open access journal from MDPI · 2026Article
- Regulatory roles of intestinal CD4Gut microbes · 2025Review
- The interplay between host immunity andmBio · 2025Review
- DOCK8 in T cells promotes Th17 and Treg cell functionality to restrain mucosal mast cells and limit susceptibility to oral anaphylaxis.Immunity · 2025Article
- Mechanisms ofFrontiers in cellular and infection microbiology · 2025Review
- Harnessing the human gut microbiota: an emerging frontier in combatting multidrug-resistant bacteria.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
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 with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.