Integrated multi-omics highlights alterations of gut microbiome functions in prodromal and idiopathic Parkinson’s disease

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbial community compared to healthy subjects. Although alterations have been most commonly described as differential abundance of bacteria, fewer studies have focused on the functionnal aspect of these changes. Causal and mechanistic connections between the gut microbiome and PD pathogenesis remain elusive, but could include molecules that influence inflammation or neuronal α-synuclein aggregation. Here, we perform an integrated multi-omic analysis of fecal samples from patients with PD or a prodrome thereof (idiopathic REM sleep behaviour disorder, iRBD) compared to healthy controls. We reveal 11 metabolites significantly different between the three groups, amongst which β-glutamate was increased in PD and prodromal PD, and correlated with the transcriptional activities of Methanobrevibacter smithii and Clostridium spp. In addition, we identified a decrease in transcript for motilty and flagellar assembly pathways in keystone bacteria such as Roseburia and Agathobacter. Our study highlights the apparent disruption of microbial gene expression in PD, in particularly gene associated to mobility which can impact the immune system, and the neuro-inflammation involved in PD.