Genes & diseasesOct 23, 2026

Gut bacteria-produced histamine and serotonin may promote new blood vessel growth in the brain’s blood supply system in moyamoya disease

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 24, 2026

Abstract

Enrichment of Bifidobacterium pseudocatenulatum is closely associated with elevated microbial-derived histamine and serotonin in Moyamoya disease.

Moyamoya disease is characterized by arterial narrowing and the formation of new blood vessels.
Elevated levels of histamine and serotonin have been linked to the presence of B. pseudocatenulatum in individuals with Moyamoya disease.
In mice, chronic exposure to B. pseudocatenulatum led to disruptions in gut barrier function and increased production of histamine and serotonin.
These microbial metabolites were associated with systemic inflammation and activation of pathways related to blood vessel growth.
Direct introduction of histamine or serotonin into mice resulted in vascular changes similar to those seen in Moyamoya disease.
The findings suggest a complex interaction between gut microbiota and vascular health, indicating potential avenues for non-invasive diagnostics and therapies.

Simplified

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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Gut bacteria-produced histamine and serotonin may promote new blood vessel growth in the brain’s blood supply system in moyamoya disease

Abstract

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