Integrative microbiome and functional profiling decodes pro-inflammatory gut microbiome signatures in South Indian patients with Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by α-synuclein aggregation in dopaminergic neurons. Emerging evidence implicates gut microbiota dysbiosis in PD-associated inflammation through the gut microbiota-brain axis (GMBA). As gut microbial composition varies geographically, population-specific studies are essential to understand this relationship. The present study employed 16S rRNA gene amplicon sequencing to characterize the gut microbiome of PD patients and healthy controls (HCs) from Kerala. Significant differences in microbial diversity and taxonomic composition were observed. PD patients exhibited increased abundances of pro-inflammatory genera, including Akkermansia, Bifidobacterium, Escherichia-Shigella, Collinsella, Eggerthellaceae_insertae_sedis_genus, Intestinimonas, and Enterobacterales_unclassified , alongside reduced levels of anti-inflammatory genera such as Bacteroides, Lachnospira, Agathobacter, Prevotella, and Erysipelotrichaceae UCG-003 . Predictive functional profiling indicated alterations in pathways related to neurotransmitter metabolism, including dopaminergic, glutamatergic, and GABAergic metabolism, as well as amino acid, polyamine, nucleotide, and energy metabolism. Integrative network analysis further linked PD-enriched taxa with dysregulated metabolic pathways, suggesting functional interactions between microbial composition and metabolic potential. These findings provide the first comprehensive insights into gut microbial alterations in a South Indian PD cohort, identify candidate microbial signatures associated with PD, and offer an exploratory framework for future multi-omics studies to validate microbiome-related mechanisms in PD pathophysiology.