{
  "abstract": "Parkinson’s disease (PD) is a systemic disorder linked to gut dysbiosis, yet key microbiota-regulated metabolites remain unclear. Here, we observe elevated taurochenodeoxycholic acid (TCDCA) in patients with PD that correlates with disease severity. Reduced bile salt hydrolase (BSH) gene abundance correlates inversely with circulating TCDCA, consistent with altered bile acid deconjugation. Exogenous TCDCA correlates with aggravated motor and gastrointestinal deficits, impaired blood-brain barrier (BBB) integrity, and accelerated dopaminergic neurodegeneration in a PD mouse model. Mechanistically, TCDCA links to TGR5 signaling activation in vascular smooth muscle cells (VSMCs), alongside PKCα-dependent mitochondrial apoptosis and BBB disruption. VSMC-specific Tgr5 deletion coincides with neurovascular protection. Supplementation with a BSH-high Lactobacillus reuteri strain reduces TCDCA concentrations, improves gut and BBB integrity, mitigates inflammation, and alleviates PD-like phenotypes in a BSH-dependent manner. These data support a gut-BBB-brain axis linked to PD, identifying TCDCA as a candidate pathological marker.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China",
    "Institute for Drug Evaluation, Peking University Health Science Center, Beijing 100191, China",
    "Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, China",
    "Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, China",
    "School of Basic Medicine, Qingdao university, Qingdao, Shandong 266071, China",
    "Department of Neurology, Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing 100191, China",
    "The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Health Science Center, Peking University, Beijing 100191, China",
    "Research Center for Cardiopulmonary Rehabilitation, University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital), School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao 266113, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhe Zhao"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Yixuan Liu"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Wen Ma"
    },
    {
      "affs": [
        6
      ],
      "name": "Gaofei Hu"
    },
    {
      "affs": [
        6
      ],
      "name": "Jincen Hao"
    },
    {
      "affs": [
        5
      ],
      "name": "Chaobo Bai"
    },
    {
      "affs": [
        5
      ],
      "name": "Jing Chen"
    },
    {
      "affs": [
        6
      ],
      "name": "Qi Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Huanhuan Cao"
    },
    {
      "affs": [
        6
      ],
      "name": "Xiaoyi Liu"
    },
    {
      "affs": [
        6
      ],
      "name": "Yujie Zhu"
    },
    {
      "affs": [
        6
      ],
      "name": "Manyuan Dong"
    },
    {
      "affs": [
        6
      ],
      "name": "Zheng Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Shenge Su"
    },
    {
      "affs": [
        7
      ],
      "name": "Rui Zhan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Huibo Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rongsheng Zhao"
    },
    {
      "affs": [
        5
      ],
      "name": "Junliang Yuan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/byq2s3pknqsbv.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103098",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710375/",
  "id": "byq2s3pknqsbv",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103098",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
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  "openalex": "W7221084609",
  "pdf_url": null,
  "pmcid": "PMC13710375",
  "pmid": "42854697",
  "published": "2026-10-09",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/byq2s3pknqsbv.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:21Z",
      "native_id": "PMC13710375",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103098"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Microbiota-regulated TCDCA associates with Parkinson’s disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice",
  "title_text": "Microbiota-regulated TCDCA associates with Parkinson’s disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:21Z",
  "url": "https://research.draconitic.com/paper/byq2s3pknqsbv",
  "venue": "Cell Reports Medicine",
  "versions": []
}