Microbiota-regulated TCDCA associates with Parkinson's disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice.

IF 14 1区医学 Q1 CELL BIOLOGY

Cell Reports Medicine Pub Date : 2026-10-09 DOI:10.1016/j.xcrm.2026.103098

Zhe Zhao, Yixuan Liu, Wen Ma, Gaofei Hu, Jincen Hao, Chaobo Bai, Jing Chen, Qi Zhang, Huanhuan Cao, Xiaoyi Liu, Yujie Zhu, Manyuan Dong, Zheng Zhang, Shenge Su, Rui Zhan, Huibo Li, Rongsheng Zhao, Junliang Yuan

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引用次数: 0

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.

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微生物调节的TCDCA与帕金森病的严重程度相关，并通过小鼠VSMC TGR5信号传导促进血脑屏障功能障碍。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.