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Peer-reviewedCC BYGenes & diseases

Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease.

  • Haiyan Tian1,2,3
  • Lilan Zhu1,2,3,4
  • Yuheng Zhang1,2,4
  • Mengwei Chen3
  • Xueying Zuo3
  • Yi Wu3
  • Hanzhen Wang1,2,3,4
  • Zheng Lv3
  • Qing Huang5,6
  • Min Wu7,8
  • Erxi Wu9,10,11
  • Jinsheng Zeng1,2,4
1 more authors
  • Xuejing Wang1,2,4
11 affiliations
  1. 1Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, Guangzhou, Guangdong 510080, China.
  2. 2National Key Clinical Department, Key Discipline of Neurology, Guangzhou, Guangdong 510080, China.
  3. 3Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
  4. 4Department of Neurology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
  5. 5Hunan Clinical Research Center for Cerebrovascular Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410028, China.
  6. 6National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410028, China.
  7. 7Drug Discovery Center, Wenzhou Institute University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325000, China.
  8. 8Department of Critical Care Medicine, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  9. 9Neuroscience Institute and Department of Neurosurgery, Baylor Scott & White Health, Temple, TX 76508, United States.
  10. 10Department of Neurosurgery, Baylor College of Medicine, Temple, TX 76508, United States.
  11. 11Baylor Research Institute, Baylor Scott & White Health, Temple, TX 76508, United States.
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Abstract

Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by arterial stenosis and compensatory neovascularization, but its upstream drivers remain poorly defined. Here, we identify Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), a traditionally probiotic species, as a context-dependent pathobiont. Integrated metagenomic and metabolomic analyses revealed enrichment of B. pseudocatenulatum in MMD, closely associated with elevated microbial-derived histamine and serotonin. In mice, chronic oral administration of B. pseudocatenulatum disrupted intestinal barrier integrity and increased gut microbial production and systemic levels of histamine and serotonin. These changes were accompanied by systemic inflammation and activation of angiogenic pathways, which together promoted MMD-relevant cerebrovascular remodeling in experimental models. Notably, direct administration of histamine or serotonin to mice reproduced key MMD-like vascular phenotypes, supporting the conclusion that these microbial metabolites are sufficient to induce selected MMD-relevant vascular changes in experimental models. Our findings propose a microbial-metabolite-vascular axis and suggest that the role of specific Bifidobacterium strains may be more nuanced than previously recognized. These results provide a mechanistic framework for understanding the gut-brain axis in neurovascular pathology and nominate the microbiome and its metabolic products as potential targets for non-invasive diagnostics and precision therapeutic interventions in MMD.

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Cite

BibTeXRIS
BibTeX
@article{tian2026microbial,
  title = {{Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease.}},
  author = {Haiyan Tian and Lilan Zhu and Yuheng Zhang and Mengwei Chen and Xueying Zuo and Yi Wu and Hanzhen Wang and Zheng Lv and Qing Huang and Min Wu and Erxi Wu and Jinsheng Zeng and Xuejing Wang},
  journal = {Genes \& diseases},
  year = {2026},
  month = jun,
  doi = {10.1016/j.gendis.2026.102306},
  url = {https://europepmc.org/article/MED/42909340},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Gut microbial histamine and serotonin promote cerebrovascular angiogenesis: Evidence from moyamoya disease.
AU  - Haiyan Tian
AU  - Lilan Zhu
AU  - Yuheng Zhang
AU  - Mengwei Chen
AU  - Xueying Zuo
AU  - Yi Wu
AU  - Hanzhen Wang
AU  - Zheng Lv
AU  - Qing Huang
AU  - Min Wu
AU  - Erxi Wu
AU  - Jinsheng Zeng
AU  - Xuejing Wang
PY  - 2026
DA  - 2026/06/13
JO  - Genes & diseases
DO  - 10.1016/j.gendis.2026.102306
UR  - https://europepmc.org/article/MED/42909340
AB  - Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by arterial stenosis and compensatory neovascularization, but its upstream drivers remain poorly defined. Here, we identify Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), a traditionally probiotic species, as a context-dependent pathobiont. Integrated metagenomic and metabolomic analyses revealed enrichment of B. pseudocatenulatum in MMD, closely associated with elevated microbial-derived histamine and serotonin. In mice, chronic oral administration of B. pseudocatenulatum disrupted intestinal barrier integrity and increased gut microbial production and systemic levels of histamine and serotonin. These changes were accompanied by systemic inflammation and activation of angiogenic pathways, which together promoted MMD-relevant cerebrovascular remodeling in experimental models. Notably, direct administration of histamine or serotonin to mice reproduced key MMD-like vascular phenotypes, supporting the conclusion that these microbial metabolites are sufficient to induce selected MMD-relevant vascular changes in experimental models. Our findings propose a microbial-metabolite-vascular axis and suggest that the role of specific Bifidobacterium strains may be more nuanced than previously recognized. These results provide a mechanistic framework for understanding the gut-brain axis in neurovascular pathology and nominate the microbiome and its metabolic products as potential targets for non-invasive diagnostics and precision therapeutic interventions in MMD.
SN  - 2352-4820
SN  - 2352-3042
ER  -