{
  "abstract": "Anastomotic leakage (AL) remains a devastating complication after colorectal cancer resection. Proton pump inhibitors (PPIs) are widely overused perioperatively, but their impact on anastomotic healing is unknown. We investigated whether and how PPIs affect colorectal anastomotic healing. Mice underwent colorectal anastomosis after oral or intraperitoneal esomeprazole. Healing was assessed by scoring, hydroxyproline, fibronectin, Masson staining, and bacterial dissemination to the spleen. Oral or gut microbiota were depleted with antibiotics, and FMT, 16S rRNA sequencing, metabolomics, and transcriptomics were performed. Both routes of PPI impaired healing and increased splenic bacterial load, which was abrogated by depletion of oral or gut microbiota. PPI enriched oral Streptococcus anginosus (S. anginosus) in the gut. FMT from PPI-treated donors recapitulated healing impairment, whereas FMT from donors with prior oral microbiota depletion did not. Succinic acid was identified as a key secreted metabolite of S. anginosus; the healing defect was recapitulated by succinic acid alone and attenuated by pharmacological SUCNR1 antagonism. Mechanistically, succinic acid activates SUCNR1-NF-κB signaling, upregulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and MMP activities. In an exploratory clinical association analysis, high-dose PPI users exhibited elevated faecal S. anginosus and succinic acid, which correlated with serum TNF-α and IL-6. In conclusion, PPI-induced acid suppression promotes oral-to-gut enrichment of S. anginosus and increases succinic acid, activating SUCNR1-NF-κB signaling to impair anastomotic healing. These findings caution against PPI overuse and suggest the succinic acid-SUCNR1-NF-κB axis as a potential therapeutic target.",
  "abstract_shown": true,
  "affiliations": [
    "The Second Clinical Medical College, Army Medical University, Chongqing 400037, China",
    "Department of Microbiology, Army Medical University, Chongqing 400037, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaolong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuhao Jiang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kai Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Feng Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Liping Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanliang Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yiming Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuling Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangsheng Du"
    },
    {
      "affs": [
        0
      ],
      "name": "Kun Yu",
      "orcid": "0009-0009-4389-5530"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiancai Rao",
      "orcid": "0000-0002-9905-760X"
    },
    {
      "affs": [
        0
      ],
      "name": "Weidong Xiao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/deemwjpgdj8hh.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219988",
  "fulltext_url": null,
  "id": "deemwjpgdj8hh",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9988",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/deemwjpgdj8hh.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:27Z",
      "native_id": "10.3390/ijms27219988",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9988"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Proton Pump Inhibitors Promote Oral-to-Gut Enrichment of S. anginosus and Impair Anastomotic Healing via Succinic Acid-SUCNR1-NF-κB Signaling Axis",
  "title_text": "Proton Pump Inhibitors Promote Oral-to-Gut Enrichment of S. anginosus and Impair Anastomotic Healing via Succinic Acid-SUCNR1-NF-κB Signaling Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:27Z",
  "url": "https://research.draconitic.com/paper/deemwjpgdj8hh",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}