Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson’s disease based on metagenomic sequencing Original paper

What was studied?

This study investigated gender-specific alterations in the gut microbiota and their association with brain function in patients with Parkinson’s disease (PD), utilizing metagenomic sequencing and resting-state functional magnetic resonance imaging (fMRI). The primary focus was on clarifying whether there are notable differences in the composition and function of the gut microbiota between male and female PD patients, and how these differences may relate to changes in brain activity. The researchers performed deep metagenomic sequencing on fecal samples to profile the microbiota and analyzed the microbial functional pathways using gene ontology and KEGG enrichment. Resting-state fMRI was used to assess regional neural activity via the amplitude of low-frequency fluctuations (ALFF), allowing the team to explore gut-brain correlations. By linking metagenomic and neuroimaging data, the study aimed to provide mechanistic insight into the microbiota-gut-brain axis as it relates to gender disparities in PD.

Who was studied?

The study enrolled 24 patients diagnosed with Parkinson’s disease (13 males and 11 females), recruited from the Department of Neurology at the First People’s Hospital of Huai’an City, affiliated with Nanjing Medical University, China. All participants were age-, weight-, and Hoehn-Yahr (HY) stage-matched and ranged in age from 52 to 78 years. Exclusion criteria included Parkinson’s syndrome, chronic gastrointestinal disease, autoimmune diseases with gastrointestinal involvement, malignancy, and recent antibiotic use. Participants underwent assessments for body mass index, motor symptoms, anxiety, and depression, and were kept on a stable PD medication regimen. Informed consent was obtained from all subjects, and the study protocol received ethics committee approval.

Most important findings

A central finding was the identification of significant gender-specific differences in the gut microbial composition at the genus and family levels, despite the absence of notable differences in overall microbial diversity (alpha and beta diversity) between male and female PD patients. In males, the genera Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname were more abundant, and LEfSe analysis indicated male dominance of Verrucomicrobia, Akkermansiaceae, and Akkermansia. Female patients, conversely, showed increased abundance of Escherichia, Escherichia coli, and Lachnospiraceae, with a notable decrease in Propionicicella.

Functional metagenomic analysis revealed that pathways involved in sesquiterpenoid and triterpenoid biosynthesis were significantly upregulated in male patients. These secondary metabolites have been implicated in neuroprotection, suggesting a potential gender-biased microbial influence on PD pathology.

Neuroimaging results demonstrated that female PD patients had decreased ALFF values in the left inferior parietal regions compared to males, indicating reduced regional brain activity. Importantly, the abundance of Propionivibrio was positively correlated (r = 0.45, p = 0.027) with ALFF values in these regions, directly linking specific gut microbial taxa to functional changes in the brain.

Key implications

This study is the first to integrate metagenomic and fMRI analyses to elucidate gender-specific microbiota signatures and their neurofunctional correlates in PD. The findings suggest that sex differences in PD may be partially mediated by distinct gut microbial patterns, which could influence neural activity via the microbiota-gut-brain axis. The dominance of Akkermansia and Verrucomicrobia in males, and Escherichia and Lachnospiraceae in females, supports the notion of gender as a critical variable in PD-associated dysbiosis. The positive association between Propionivibrio abundance and parietal brain activity further highlights the potential for gut microbiota to modulate neurological function in a sex-dependent manner. These insights underscore the need for personalized, gender-informed approaches in PD management and suggest that microbial signatures could serve as biomarkers or therapeutic targets. However, the small sample size and lack of healthy controls warrant caution; larger, longitudinal studies are needed to validate these findings and elucidate underlying mechanisms.

Citation

Zhang M, Zhai Z, Yang B, He L, Wang J, Dai W, Xue L, Yang X, Feng Y, Wang H. Exploring the alteration of gut microbiota and brain function in gender-specific Parkinson’s disease based on metagenomic sequencing. Front Aging Neurosci. 2023;15:1148546. doi:10.3389/fnagi.2023.1148546