GUT MICROBIOTE DISTINCTIVE FEATURES IN PARKINSON DISEASE: FOCUS ON DUODOPA AND OTHER ANTIPARKINSONIAN DRUGS

Background: Recent data suggest that imbalances in the composition of the intestinal microbiome could trigger and / or exacerbate the progression of PD. It is also hypothesized that such modifications are influenced by extrinsic factors and the specific effect of Levodopa (LD) and in particular of LD-carbidopa intestinal gel (LCIG) has not been evaluated so far Objective: The aim of this study was to confirm whether the faecal microbiota of PD patients differs from that of control subjects and to identify the effect of LD and LCIG on the gut microbiota composition. Methods: We analyzed the gut microbiota in 107 PD cases and 25 healthy controls by next-generation sequencing of the variable V3 and V4 regions of the 16S rRNA gene. Subjects were divided in three treatment groups, LD-Group, LCIG-Group and Naïve-Group, patients who have not assumed any medicaments containing LD at the moment of recruitment. The fecal samples were collected and stored at -80°C before DNA extraction, library preparation and sequencing by MiSeq platform (Illumina). Statistical analyses were performed including the corrections for several potential confounders and multiple comparisons. Results: Independent microbial signatures were detected for treated and untreated PD versus Control-Group. After correction for confounders LD-Group showed a reduction of Bacteroides and Firmicutes phyla, while Veillonella genus (Firmicutes) and Serratia entomophila (Proteobacteria) were increased. LCIG-Group showed an increase in the abbundance in Proteobacteria, a reduction of Brevibacteriaceae and of Blautia. LCIG-Group showed a significant higher abbundance of Enterobacteriaceae family, Escherichia and Serratia genera compared to LD-Group. Conclusion: Our results suggest that LD and mostly its intraudodenal injection (LCIG) might significantly influence microbiota composition with a potential pro-inflammatory effect. Further studies with larger cohorts and high-resolution sequencing methods are required to better define the causal link between these changes and PD pathogenesis.