ArticlePLoS pathogens2021
Bile acid-independent protection against Clostridioides difficile infection.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed.
- Microbiome-based therapeutics forGut microbes · 2026Review
- Pleiotropic roles of microbial bile acid metabolism in intestinal health and diseases.Cell host & microbe · 2026Review
- A programmed reset mechanism primesScience advances · 2026Article
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- Ecological and dietary strategies to constrain Clostridioides difficile.Cell host & microbe · 2026Review
- Apple Pomace Fermented with Non-International journal of molecular sciences · 2026Article
- Bile acid dependent attenuation of toxin mediated disease is independent of colonization resistance againstbioRxiv : the preprint server for biology · 2026Article
- Successful fecal microbiota transplants in post-antibiotic treated recurrentGut microbes reports · 2026Article
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- The swine IsoLoop model of the gut host-microbiota interface enables intra-animal treatment comparisons to advance 3R principles.Gut microbes · 2025Article
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- Experimental glycopeptide antibiotic EVG7 prevents recurrent Clostridioides difficile infection by sparing members of the Lachnospiraceae family.Nature communications · 2025Article
- Unravelling three-way interactions betweenJournal of medical microbiology · 2025Review
- Microbiota Gut-Brain Axis and Autism Spectrum Disorder: Mechanisms and Therapeutic Perspectives.Nutrients · 2025Review
- The interplay between host immunity andmBio · 2025Review
- Amino acid competition shapes Acinetobacter baumannii gut carriage.Cell host & microbe · 2025Article
- Phenotypic analysis of variousApplied and environmental microbiology · 2025Article
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- Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- EmergingmSystems · 2025Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Clostridioides difficile infections occur upon ecological / metabolic disruptions to the normal colonic microbiota, commonly due to broad-spectrum antibiotic use. Metabolism of bile acids through a 7α-dehydroxylation pathway found in select members of the healthy microbiota is regarded to be the protective mechanism by which C. difficile is excluded. These 7α-dehydroxylated secondary bile acids are highly toxic to C. difficile vegetative growth, and antibiotic treatment abolishes the bacteria that perform this metabolism. However, the data that supports the hypothesis that secondary bile acids protect against C. difficile infection is supported only by in vitro data and correlative studies. Here we show that bacteria that 7α-dehydroxylate primary bile acids protect against C. difficile infection in a bile acid-independent manner. We monoassociated germ-free, wildtype or Cyp8b1-/- (cholic acid-deficient) mutant mice and infected them with C. difficile spores. We show that 7α-dehydroxylation (i.e., secondary bile acid generation) is dispensable for protection against C. difficile infection and provide evidence that Stickland metabolism by these organisms consumes nutrients essential for C. difficile growth. Our findings indicate secondary bile acid production by the microbiome is a useful biomarker for a C. difficile-resistant environment but the microbiome protects against C. difficile infection in bile acid-independent mechanisms.
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