Peer-reviewedCC BY-NC 4.0Cell Reports Medicine
Microbiota-regulated TCDCA associates with Parkinson’s disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice
8 affiliations
- 1Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
- 2Institute for Drug Evaluation, Peking University Health Science Center, Beijing 100191, China
- 3Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100083, China
- 4Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing 100083, China
- 5School of Basic Medicine, Qingdao university, Qingdao, Shandong 266071, China
- 6Department 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
- 7The 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
- 8Research 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
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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BibTeX
@article{zhao2026microbiotaregulated,
title = {{Microbiota-regulated TCDCA associates with Parkinson’s disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice}},
author = {Zhe Zhao and Yixuan Liu and Wen Ma and Gaofei Hu and Jincen Hao and Chaobo Bai and Jing Chen and Qi Zhang and Huanhuan Cao and Xiaoyi Liu and Yujie Zhu and Manyuan Dong and Zheng Zhang and Shenge Su and Rui Zhan and Huibo Li and Rongsheng Zhao and Junliang Yuan},
journal = {Cell Reports Medicine},
year = {2026},
month = oct,
doi = {10.1016/j.xcrm.2026.103098},
url = {https://doi.org/10.1016/j.xcrm.2026.103098},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Microbiota-regulated TCDCA associates with Parkinson’s disease severity and promotes BBB dysfunction through VSMC TGR5 signaling in mice
AU - Zhe Zhao
AU - Yixuan Liu
AU - Wen Ma
AU - Gaofei Hu
AU - Jincen Hao
AU - Chaobo Bai
AU - Jing Chen
AU - Qi Zhang
AU - Huanhuan Cao
AU - Xiaoyi Liu
AU - Yujie Zhu
AU - Manyuan Dong
AU - Zheng Zhang
AU - Shenge Su
AU - Rui Zhan
AU - Huibo Li
AU - Rongsheng Zhao
AU - Junliang Yuan
PY - 2026
DA - 2026/10/09
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.103098
UR - https://doi.org/10.1016/j.xcrm.2026.103098
AB - 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.
SN - 2666-3791
ER -