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Carr, AV; Baliga, NS; Diener, C; Gibbons, SM.
Personalized Clostridioides difficile colonization risk prediction and probiotic therapy assessment in the human gut
CELL SYST. 2025; 16(8): 101367 Doi: 10.1016/j.cels.2025.101367
Web of Science PubMed FullText FullText_MUG

 

Führende Autor*innen der Med Uni Graz
Diener Christian
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Abstract:
Clostridioides difficile (C. difficile) colonizes up to 40% of community-dwelling adults without causing disease but can eventually lead to infection (C. difficile infection [CDI]). There has been a lack of focus on how to prevent colonization and facilitate the successful clearance of C. difficile prior to the emergence of CDI. We show that microbial community-scale metabolic models (MCMMs) accurately predict C. difficile colonization susceptibility in vitro and in vivo, offering mechanistic insights into microbiota-specific interactions involving metabolites like succinate, trehalose, and ornithine. MCMMs reveal distinct C. difficile metabolic niches-two growth-associated and one non-growth-associated-observed across 15,204 individuals from five cohorts. We further demonstrate that MCMMs can predict personalized C. difficile growth suppression by a probiotic cocktail designed to replace fecal microbiota transplants (FMTs) for the treatment of recurrent CDI, and we identify new probiotic targets for future validation. MCMMs represent a powerful framework for predicting pathogen colonization and assessing probiotic efficacy across diverse microbiota contexts. A record of this paper's transparent peer review process is included in the supplemental information.

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