{
  "abstract": "Antibiotic disruption of gut microbiota creates opportunities for toxigenic Clostridioides difficile. One strategy is to occupy this niche with a non-toxigenic or weakly virulent strain, but even strains that cause little disease may fail to compete during pathogen challenge. We screened 21 sequence type 1 (ST1) isolates for their ability to protect mice co-colonized with toxigenic VPI10463, separating disease potential from protection. Some strains, such as ST1-75, caused little disease and protected, whereas others, such as ST1-68, caused little disease but failed to protect. Metabolomics showed that ST1-75 depleted more proline than ST1-68, whereas another protective strain, ST1-6, had a different metabolic profile; both protective strains nevertheless responded to many substrates. Substrate-utilization profiling revealed that protection across the 21 isolates correlated with amino-acid overlap with VPI10463, but not overall nutrient overlap or shared genome-encoded protein families. Relative amino-acid access explained variation beyond mono-colonization disease potential, and a consumer-resource model showed how nutrient overlap together with additional resource access can support persistence during competition. Additional experiments support that ST1-mediated protection occurs even in the absence of mature B and T cells. These findings distinguish low disease potential from protection, link protection to strain competition, and identify relative resource access as an informative phenotype for prioritizing strains for biotherapeutic testing.",
  "abstract_shown": true,
  "affiliations": [
    "Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "V. Mishra"
    },
    {
      "name": "K. Sia"
    },
    {
      "name": "C. Lindberg"
    },
    {
      "name": "S. Sharma"
    },
    {
      "name": "M. Wu"
    },
    {
      "name": "A. Djukovic"
    },
    {
      "name": "H. Jeong"
    },
    {
      "name": "M. Kamboj"
    },
    {
      "name": "Q. Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "J. B. Xavier"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cg58ecg736a6f.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.02.756234",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756234v1.full",
  "id": "cg58ecg736a6f",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756234v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|Clostridium difficile and Clostridium perfringens research"
    ]
  ],
  "openalex": "W7218886032",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756234v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-02",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cg58ecg736a6f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:56Z",
      "native_id": "10.64898/2026.10.02.756234",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.02.756234v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Resource-access breadth marks protective strains against toxigenic Clostridioides difficile",
  "title_text": "Resource-access breadth marks protective strains against toxigenic Clostridioides difficile",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:56Z",
  "url": "https://research.draconitic.com/paper/cg58ecg736a6f",
  "venue": "bioRxiv",
  "versions": []
}