Association of elevated Trimethyl amine and its metabolites with Gut microbial dysbiosis in Parkinson’s Disease. (22028)
Multiple cohort studies indicate that gut microbiota composition is significantly altered in people with Parkinson’s disease (PD). Despite this, pathological significance of the gut microbial dysbiosis remains elusive. Gastrointestinal dysfunction, often preceding clinical PD diagnosis, is commonly observed in PD patients. In this study, we evaluated the changes in gut microbial metabolites in PD patient biofluids and used functional metagenomics to determine changes in microbial composition and pathways in PD patients compared to an age-matched healthy cohort. Our analysis identified notable shift in multiple microbial metabolites, including Trimethylamine (TMA), a brain-permeable metabolite of bacterial origin with a positive association with the rate of PD progression and cognitive decline. TMA and its metabolites were also altered in both PD patient blood and urine in a cohort of healthy (n =31) and PD (n = 31) patients. We also uncovered elevated levels of Formaldehyde (FA), in our PD cohort. Our functional metagenomics studies demonstrate for the first time that TMA-generating bacteria, as well as bacterial enzymatic pathways responsible for its generation to be increased in PD. We also uncovered a trend towards loss of beneficial bacteria which produce anti-inflammatory metabolites, such as butyrate, in PD. Our results provide novel insights into how gut dysbiosis and microbial metabolism can drive PD.