This study aimed to systematically elucidate the molecular mechanisms underlying PD-associated brain-gut dysfunction through multi-omics analyses and to evaluate the therapeutic potential of combined Deep Brain Stimulation (DBS) and Brain-Computer Interface (BCI) interventions. Transcriptomic and 16S rRNA datasets from Gene Expression Omnibus (GEO) and Sequence Read Archive (SRA) were integrated and analyzed using DESeq2, limma, Gene Set Enrichment Analysis (GSEA), and PICRUSt2 to identify disrupted pathways and microbial functional features. In the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model, four groups (Normal, MPTP, MPTP + DBS, and MPTP + DBS+BCI) were assessed using behavioral testing, Local Field Potentials (LFP) recordings, molecular assays, and histological analysis. The findings revealed synaptic damage and metabolic pathway disruptions in PD brains, accompanied by reduced abundance of Short-Chain Fatty Acid (SCFA)-producing gut microbes. Combined DBS and BCI markedly improved motor deficits, suppressed aberrant β oscillations, restored gut barrier integrity and microbial homeostasis, and reduced pathological α-synuclein (αSyn) aggregation. Collectively, these results demonstrate that DBS + BCI is associated with improvements across neural, microbial and inflammatory readouts, supporting a correlative brain-gut-immune framework.
Song et al. (2026) studied this question.