{
  "abstract": "Clostridioides difficile is a major cause of healthcare associated infections. C. difficile infection (CDI) is a toxin-mediated disease driven by the secretion of two large protein toxins, Toxin A (TcdA) and Toxin B (TcdB). TcdA and TcdB cause neurogenic inflammation that can contribute to intestinal inflammation in rat and mouse models. Substance P (SP), a potent vasoactive neuropeptide, is a major contributor to C. difficile toxin induced inflammation in animal models. SP acts on multiple receptors including the high affinity receptor NK1-R, and lower affinity receptors (Mrgprb2 and NK2-R). Through in vivo mouse infection models, we confirmed the effects of SP in hypervirulent C. difficile are largely mediated by the neurokinin-1 receptor (NK1-R), the high affinity receptor for SP. Through genetic mice that lack mast cells (cKitW-sh) we determined that mast cells which respond to SP in certain kinds of neurogenic inflammation appear dispensable for inflammation caused by C. difficile infection. We explored the role of NK1-R antagonists in a retrospective study of a large clinical cohort. We determined that, after propensity matching, NK1-R antagonists were associated with a significant survival benefit and that patients treated with NK1-R antagonists showed evidence of reduced vascular inflammation (increased serum albumin). Together these data suggest blocking SP activity through antagonism of NK1-R with small molecule inhibitors may be a useful strategy for adjunctive treatment during C. difficile infection.",
  "abstract_shown": true,
  "affiliations": [
    "University of Pittsburgh School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "L. Zhao"
    },
    {
      "name": "M. Liu"
    },
    {
      "name": "S. Wang"
    },
    {
      "name": "M. A. Musser"
    },
    {
      "name": "A. Shepherd"
    },
    {
      "name": "J. Zhang"
    },
    {
      "name": "M. Whalen"
    },
    {
      "name": "D. Binion"
    },
    {
      "name": "M. Rao"
    },
    {
      "name": "M. Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Manion"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/825e9hhzygysp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.06.749186",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749186v1.full",
  "id": "825e9hhzygysp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749186v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|Clostridium difficile and Clostridium perfringens research"
    ]
  ],
  "openalex": "W7211972431",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749186v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/825e9hhzygysp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:00Z",
      "native_id": "10.64898/2026.09.06.749186",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.06.749186v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Neurokinin 1 receptor blockade is associated with increased survival of patients with C. difficile infection",
  "title_text": "Neurokinin 1 receptor blockade is associated with increased survival of patients with C. difficile infection",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:00Z",
  "url": "https://research.draconitic.com/paper/825e9hhzygysp",
  "venue": "bioRxiv",
  "versions": []
}