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

Authors#

Rémy Villette, Julia Ortis Sunyer, Polina Novikova, Velma Aho, Viacheslav Petrov, Oskar Hickl, Susheel Bhanu Busi, Charlotte De Rudder, Benoît Kunath, Anna Buschart, Jean-Pierre Trezzi, Rashi Halder, Christian Jäger, Laura Lebrun, Annegrät Daujeumont, Sebastian Schade, Annette Janzen, Nico Jehmlich, Martin Von Bergen, Cedric Christian Laczny, Patrick May, Claudia Trenkwalder, Wolfgang Oertel, Brit Mollenhauer, Paul Wilmes

Abstract#

Individuals with Parkinson’s disease (PD) exhibit differences in their gut microbiomes’ composition compared to healthy controls (HC). The functional consequences of these differences remain unclear. Here we use an integrated multi-omics approach to resolve the functional activities of the gut microbiome in prodromal PD (idiopathic REM sleep behavior disorder, iRBD) and PD compared to HC. Meta-metabolomic analyses identified 11 metabolites that were differentially abundant in PD or iRBD. These differences guided our subsequent comparisons. Amongst the identified metabolites, β-glutamate was significantly increased in individuals with PD or iRBD, and correlated with the transcriptional activity of Akkermansia, Methanobrevibacter and Clostridium. We specifically identified differences in transcripts related to glutamate metabolism that were linked to a decrease in flagellar assembly and chemotaxis transcripts expressed by specific taxa in PD. Our integrated multi-omics data highlights multifactorial alterations of structure and function in PD with disrupted functions linked to disease pathways.