ArticleNature microbiology2025
Structure-guided design of a synthetic bile acid that inhibits Clostridioides difficile TcdB toxin.
Article in Nature microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed.
- Goat Bile Acid and Clostridium butyricum Exert a Synergistic Effect in Enhancing the Therapeutic Efficacy Against Diarrhea Induced by Escherichia coli Infection.Probiotics and antimicrobial proteins · 2026Article
- The impact of TcdB conformational dynamics on vaccination against Clostridioides difficile.PLoS pathogens · 2026Article
- Probiotic interventions maintain intestinal barrier function and alleviate necrotizing enterocolitis by inhibiting ferroptosis in intestinal PMN-MDSCs.Cell death & disease · 2026Article
- Bile acid dependent attenuation of toxin mediated disease is independent of colonization resistance againstbioRxiv : the preprint server for biology · 2026Article
- Advances in research on the effects of bile acids and their receptors on intestinal function.Frontiers in nutrition · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal bile acids are a family of host and microbiota metabolites that can directly inhibit toxin B (TcdB), the primary virulence factor of Clostridioides difficile that causes infectious diarrhoea and colitis. However, the mechanism underlying the inhibition is unclear. Here we used cryogenic electron microscopy and determined the structure of TcdB bound to inhibitory bile acids cholic acid (methyl ester) and taurochenodeoxycholic acid at 2.9 Å and 3.3 Å resolution, respectively. These structures revealed that bile acids lock the C-terminal CROP domain of TcdB in a conformation that allosterically masks the two receptor-binding sites and prevents target cell recognition. Guided by the structure, we synthesized gut-restricted bile acid derivatives, designed to evade the bile acid reuptake transporters within the gut. One of the derivatives, sBA-2, was retained within the gut upon oral dosing and protected mice from toxin-induced C. difficile disease pathology. Our study uncovers the structural basis of inhibition of TcdB by bile acids and its analogues, paving the way for the development of orally deliverable therapeutics against C. difficile.
Indexed as
Identifiers
41254394What OpenQuestion holds
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.