Gut Microbiome Alterations Drive Distinct Metabolic Expression Patterns in a Cohort of Italian Patients with Parkinson's Disease

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson, although a cause-effect relationship yet remains to be established. Herein, the composition of the microbiota in fecal extracts of 64 patients with Parkinson's disease and 51 controls was determined using a next generation sequencing approach. A hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool was also performed. A significant decrease in the abundance of taxa belonging to the phylum Firmicutes, particularly in the Lachnospiraceae family was detected in the patient group. Key members of the Lachnospiraceae family, such as the genus Blautia and some related species, were significantly reduced in patients compared to controls. Moreover, consistent with depletion of short chain fatty acids-producing bacteria, genera and species within the Lachnospiraceae family (Butyrivibrio, Pseudobutyrivibrio, Coprococcus, Roseburia and Roseburia faecis) were also decreased. Interestingly, the relative abundance of Brevibacteriaceae and Lachnospiraceae was positively associated with tremor-dominant phenotype, whereas abundance of Enterobacteriaceae and Escherichia was positively associated with non-TD phenotypes. Finally, the functional prediction of gut metagenome composition in patients, in comparison with those of healthy controls, showed the presence of 81 significantly altered metabolic pathways. In particular, there was a significant increase of most pathways of the amino acids and lipids metabolisms, of other secondary metabolites, and in the metabolism and biodegradation of xenobiotics.