{
  "abstract": "Necrotizing enterocolitis (NEC) is a disease in preterm infants associated with an increased abundance of Enterobacteriaceae. FimH, a mannose-binding adhesin on Enterobacteriaceae type 1 fimbriae, mediates mucosal attachment and TLR4-dependent inflammatory cascades. We evaluated the safety, pharmacokinetics, and efficacy of an oral FimH inhibitor (Sibofimloc) to reduce Enterobacteriaceae colonization and prevent NEC in preterm piglets. We performed a 9-d dose-escalation safety study (10, 25, 50 mg/kg BID) assessing absorption and tolerability and a 10-d randomized efficacy study. Piglets in the efficacy study received an infant formula diet with or without oral sibofimloc (40 mg/kg BID), or donor human milk (DHM) as a healthy control. NEC incidence, tissue histopathology, and gut microbiota composition via metagenomic whole-genome sequencing (WGS) were evaluated. Systemic exposure data reveal that sibofimloc was dose-dependently absorbed, while plasma levels decreased from postnatal day 2 to day 8, indicating reduced drug absorption with maturation of the intestinal barrier. Treatment with sibofimloc did not reduce NEC incidence (100% in sibofimloc in formula controls) or severity, whereas DHM-fed piglets experienced 0% NEC. Sibofimloc-treated animals exhibited significantly reduced crypt depths, demonstrating heightened mucosal injury and impaired regenerative capacity. WGS revealed that sibofimloc-treated animals maintained a gut luminal microbiota composition similar to untreated formula controls, dominated by Clostridium perfringens (C. perfringens). Selective targeting of FimH-expressing Enterobacteriaceae was insufficient to prevent NEC or alter the gut microbiota in this preterm piglet model, underscoring the complexity of NEC-associated microbial communities and suggesting that additional microbial targets and other colonization mechanisms may contribute to disease development.",
  "abstract_shown": true,
  "affiliations": [
    "USDA/ARS Children's Nutrition Research Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "V. Melendez Hebib"
    },
    {
      "name": "B. Earls"
    },
    {
      "name": "B. Stoll"
    },
    {
      "name": "C. Vonderohe"
    },
    {
      "name": "G. Guthrie"
    },
    {
      "name": "H. J. Haiser"
    },
    {
      "name": "M. Paton"
    },
    {
      "name": "S. Balani"
    },
    {
      "name": "M. Hesse"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Burrin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9c4ew11vt5emz.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.758546",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758546v1.full",
  "id": "9c4ew11vt5emz",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758546v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2916|Infant Nutrition and Health"
    ]
  ],
  "openalex": "W7221626554",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758546v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9c4ew11vt5emz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:38Z",
      "native_id": "10.64898/2026.10.12.758546",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758546v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Pharmacokinetics and Efficacy of the FimH Inhibitor Sibofimloc in Preventing Necrotizing Enterocolitis in Preterm Piglets",
  "title_text": "Pharmacokinetics and Efficacy of the FimH Inhibitor Sibofimloc in Preventing Necrotizing Enterocolitis in Preterm Piglets",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:38Z",
  "url": "https://research.draconitic.com/paper/9c4ew11vt5emz",
  "venue": "bioRxiv",
  "versions": []
}