The present study aims to confirm the role of faecal microbiome in a large cohort of PD patients, focusing on the evaluation of a possible specific independent effect of antiparkinsonian medications. To date, no study has assessed the effect of Levodopa (LD) infused directly in the intestine (Levodopa-carbidopa intestinal gel, Duodopa) on gut microbiome. Thus we aimed at identifying the possible effect of LD and its intraduodenal infusion (Duodopa) in modifying gut microbiome composition.. Gut microbiote distinctive features inParkinson disease: focus on Duodopa and other antiparkinsonian drugs

Background: There is growing evidence that dysbiosis of the gut microbiota is associated with PD. However, the specific effect of levodopa (LD) and especially of Levodopa-carbidopa intestinal gel (Duodopa) has not been assessed 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 Duodopa 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, Duodopa-Group and Naïve-Group, patients who have not assumed any medicaments containing Levodopa 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.Duodopa-Group showed an increase in the abbundance in Proteobacteria, a reduction of Brevibacteriaceae and of Blautia. Duodopa-Group showed a significant higher abbundance of Enterobacteriaceae family, Escherichia and Serratia genera compared to LD-Group.Conclusion: The present results support the potential role of gut microbiota in the pathophysiology of PD. In addition, even if further evaluations are needed, our results lead us to suggest, for the first time, that Levodopa and mostly its intraudodenal injection (Duodopa) might significantly influence microbiota composition, with a specific potential pro-inflammatory and harmful effect.