Objective: The aim of this work was to study the microbiome of PD patients, studying the effect of dopaminergic drugs mainly focusing on the effect of levodopa (LD) and its direct injection to the bowel, Levodopa Carbidopa Intrajejunal Gel (LCIG).
Background: Recent data suggest that imbalances in the composition of the intestinal microbiome could trigger and/or exacerbate the progression of PD. They also suggest a modulating role on microbiome composition of some antiparkinsonian drugs.
Method: The composition of the microbiota in fecal extracts of 107 PD patients and 25 controls was determined. PD patients were classified in three different treatment groups: patients on oral LD (LD-Group) (n= 46), patients under LCIG (LCIG-Group) (n= 38), and patients without medicaments at the moment of recruitment (Naïve-Group) (n = 23). Microbiota was studied by 16S rRNA next-generation gene sequencing of DNA extracted from stool and a direct metabolomic analysis was conducted.
Results: 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 also showed a significant higher abbundance of Enterobacteriaceae family, Escherichia and Serratia genera compared to LD-Group. We identified several metabolite-players correlated to these gut microbiota alterations. The metabolic changes included SCFAs, lipids, fatty acids, polyamines, vitamin, polyphenol and amino acids.
Conclusion: Our results suggest that LD and mostly its intraudodenal injection (LCIG) might significantly influence microbiota composition with a potential pro-inflammatory effect. The LD-Group and LCIG-Group were closely associated to a decrease of anti-inflammatory metabolites and at the same time to an increase of pro-inflammatory bacterial products. Further studies with larger cohorts and high-resolution sequencing methods are required to better define the causal link between these changes and PD pathogenesis.
References: Scheperjans F et al Mov Disord. 2015 Mar;30(3):350-8 Hill-Burns et al Mov. Disord. 32, 739–749
To cite this abstract in AMA style:M. Melis, V. Oppo, S. Vascellari, M. Fabbri, M. Sarchioto, D. Murgia, M. Zibetti, L. Lopiano, A. Manzin, G. Cossu. Gut Microbiote Distinctive Features and Microbiota-Metabolome Profile in Parkinson’s Disease: Focus on Levodopa and LCIG [abstract]. Mov Disord. 2020; 35 (suppl 1). https://www.mdsabstracts.org/abstract/gut-microbiote-distinctive-features-and-microbiota-metabolome-profile-in-parkinsons-disease-focus-on-levodopa-and-lcig/. Accessed December 6, 2023.
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