Cross-cohort integration of gut dysbiosis and peripheral immune transcriptomics identifies candidate gut–immune modules in Parkinson's disease
Cross-cohort integration of gut dysbiosis and peripheral immune transcriptomics identifies candidate gut–immune modules in Parkinson's disease
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Original abstract
Gut dysbiosis and peripheral immune activation have been implicated in Parkinson's disease (PD), but cross-cohort integrative analyses remain limited. We performed a genus-level random-effects meta-analysis of eight published 16S rRNA gut microbiome cohorts from the PD16SData repository and integrated results with targeted whole-blood neuroimmune transcriptomics from GSE165082, followed by gene-level evaluation in GSE99039. Microbiome meta-analysis identified 75 genera differing between PD and control groups, including depletion of butyrate-producing Lachnospiraceae taxa and enrichment of oral-associated inflammatory genera. Exploratory blood transcriptomics identified nominal C1QA/C1QB downregulation and IFNG, TLR2, PTPRC, and IL18R1 upregulation; no genes reached genome-wide FDR significance. In GSE99039, SNCA, TLR4, NLRP3, and IL18R1 showed statistically significant concordant directionality. A 29-gene candidate gene-panel model showed modest discrimination only (cross-validated AUC = 0.574 ± 0.037), supporting pathway prioritisation rather than diagnostic application. These findings nominate a gut–immune inflammatory axis involving TLR4, NLRP3, and IL-18 signalling as a candidate pathway for mechanistic and prospective validation in PD.