Human gut microbiome gene co-expression network reveals a loss in taxonomic and functional diversity in Parkinson′s disease

Alterations of gut microbiome structure have been observed in a panoply of human diseases including neurodegeneration. However, the ecological and functional deficits of microbiome dysbiosis have yet to be understood. Here, using integrated multi-omics (metagenomics and metatranscriptomics), we resolve microbiome gene co-expression networks in individuals with Parkinson′s disease (PD) and healthy individuals. We uncover network modules with high closeness and degree centrality that represent core ecological functions, and identify key features lost in PD. More specifically, we observe a significant depletion in specific functions including secondary bile acid biosynthesis and flagellar assembly (FA) in PD. Strikingly, most hub genes, particularly those involved in bacterial microcompartments (BMCs) and FA, are predominantly found in healthy individuals. Blautia and Anaerobutyricum genera are the main contributors to these functions, showing significantly lower expression of BMC genes in PD. Additionally, we identify a strong correlation between the expression of BMC and FA genes, but also an apparent dysregulation in cross feeding between commensals in PD. Importantly, gene expression in PD was tied to reduced diversity in expressed genes, whereas in healthy individuals, higher expression levels were linked to higher diversity. Our findings reveal disruptions in key gut metabolic functions at both functional and taxonomic levels, potentially driving disease progression. Notably, we identify crucial microbiome-wide ecological features that should be restored in future gut microbiome rewilding efforts.