Decreased Lactococcus lactis and propionic acid in feces of patients with Moyamoya disease: Possible implications of immune dysregulation.

Introduction: Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive steno-occlusive lesions in the terminal portion of the internal carotid artery. Despite its unknown etiology, immune dysregulation is regarded as a critical trigger for delineating the pathophysiology of MMD. The gut microbiota produces short-chain fatty (SCFA) and organic acids, influencing immune regulation and vascular remodeling. We aimed to characterize the gut microbiota in patients with MMD.

Methods: Sixteen patients with MMD and sixteen healthy controls were included in this study. We performed 16S rRNA sequencing of fecal samples and analyzed microbiome diversity and composition, and quantified SCFA and organic acid levels using liquid chromatography.

Results: There were no significant differences in α- and b-diversities among feces from the MMD patients and controls. However, 16S rRNA sequencing identified defective Lactococcus lactis (0 ± 0 in the MMD patients vs. 0.026 ± 0.084 in healthy controls, p = 0.0181) and abundant Gordinobacter pamelaeae (0.030±0.039 in the patients vs. 0.001±0.005 in healthy controls, p = 0.003) are strongly linked to MMD. Propionic acid levels were significantly lower in feces of the MMD patients compared to healthy controls (0.83 ± 0.34 mg/g in the MMD patients vs. 1.20 ± 0.55 mg/g in healthy controls, p = 0.028).

Conclusion: Decreased Lactococcus lactis can result in reduced lactic acid and propionic acid levels in the feces of the patients. This imbalance in the gut microbiome and SCFA/organic acid levels could contribute to immune dysregulation underlying the vascular remodeling seen in MMD.