Objective: To investigate the difference in the gut microbiota between drug-naïve and medicated PD patients and focus on the association between gut microbiota and anti-PD medications.

Background: A series of previous researches have identified remarkable changes in the overall composition of the gut microbiota in PD patients and found that PD medications might impact on the microbiome [Table 1]. However, few evidences clarified the association of gut microbiota and the anti-PD medications.

Method: 30 drug-naïve PDs (NP), 33 medicated PDs (MP) and 33 matched normal controls (NC) were enrolled [Table 2]. To further elucidate the impact of anti-PD medications, status of the use of levodopa (n =29) and dopaminergic agonist (DA) (n=20) were considered into the group difference analysis. Microbiota composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. α-diversity and β-diversity indices, differential abundance analysis at the family, genus levels were calculated. PICRUSt was used to predict the abundances of functional categories. The divergence of metabolic pathway was deduced by KEGG pathways and further mapped using iPath 3.0.

Results: We found higher richness of α-diversity in MP patients relative to NP and NC group [Figure 1]. Significant differences between MP and NP, levodopa and non-levodopa group , DA and non-DA group in β-diversity were also detected [Figure 2]. At genus level, Phyllobacterium, Blautia and Romboutsia were typically abundant in NP compared to MP and NC. Focusing to the use of L-dopa, the increase of Lachnospira, Phreatobacter, Anaerotruncus,etc was noted while the increase of Bacteroides, Lachnospira, Lachnoclostridium, etc  was found with the use of DA [Figure 3].To clarify the underlying mechanism of microbiota changes, KEEG analysis found that the metabolic changes associated with usage of DAs could influence fatty acid biosynthesis and vitamin family B metabolism and that of levodopa could have impact on fatty acid degradation [Figure 4].

Conclusion: The anti-PD medications could change the micriobial composition of PD patients. Drug naïve PD patients present a relative increase of Blautia compared both to NC and MP, which is closely related to the production of SCFAs. DAs might take part in fatty acid biosynthesis and vitamin family B metabolism while levodopa might influence fatty acid degradation.

References: 1.Scheperjans, F., Aho, V., et al. (2015). Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord, 30(3), 350-358. doi:10.1002/mds.26069 2.Keshavarzian, A., Green, S. J., et al. (2015). Colonic bacterial composition in Parkinson’s disease. Mov Disord, 30(10), 1351-1360. doi:10.1002/mds.26307 3.Bedarf, J. R., Hildebrand, F., et al. (2017). Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naive Parkinson’s disease patients. Genome Med, 9(1), 39. doi:10.1186/s13073-017-0428-y 4.Hill-Burns, E. M., Debelius, J. W., et al. (2017). Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Mov Disord, 32(5), 739-749. doi:10.1002/mds.26942 5.Heintz-Buschart, A., Pandey, U., et al. (2018). The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord, 33(1), 88-98. doi:10.1002/mds.27105 6.Qian, Y., Yang, X., et al. (2018). Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease. Brain Behav Immun, 70, 194-202. doi:10.1016/j.bbi.2018.02.016

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MDS Abstracts - https://www.mdsabstracts.org/abstract/do-parkinsons-disease-medications-have-an-effect-on-gut-microbiome-a-case-control-study/