Gut microbiota and metabolome distinctive features in Parkinson disease: Focus on levodopa and levodopa‐carbidopa intrajejunal gel

Abstract

Background: Recent data suggest that imbalances in the composition of the gut microbiome (GM) could exacerbate the progression of Parkinson's Disease (PD). The effect of Levodopa (LD) has been poorly assessed and those of LD-carbidopa intestinal gel (LCIG) have not been evaluated so far. The aim of this study was to identify the effect of LD and, in particular, LCIG on GM and metabolome. Methods: Faecal DNA samples from 107 patients with clinical diagnosis of PD were analyzed by next-generation-sequencing of V3 and V4 regions of the 16S rRNA gene. PD patients were classified in different groups: patients on LCIG (LCIG-Group) (n= 38) and on LD (LD-Group) (n= 46). We also included a group of patients (n = 23) without antiparkinsonian medicaments (Naïve-Group). Faecal metabolic extracts were evaluated by Gas Chromatography Mass Spectrometry (GC-MS). Results: The multivariate analysis showed a significant higher abundance in the LCIG-Group of Enterobacteriaceae, Escherichia and Serratia compared to LD-Group. Compared to Naïve-Group, the univariate analysis showed a reduction of Blautia, Lachnospirae in LD-Group. Moreover, an Accepted Article This article is protected by copyright. All rights reserved increase of Proteobacteria, Enterobacteriaceae and a reduction of Firmicutes, Lachnospiraceae and Blautia was found in the LCIG-Group. No significant difference was found in the multivariate analysis of these comparisons. The LD-Group and LCIG-Group were associated to a metabolic profile linked to gut inflammation. Conclusion: Our results suggest that LD and mostly LCIG might significantly influence the microbiota composition and host/bacteria metabolism acting as stressors in precipitating a specific inflammatory intestinal microenviroment, potentially related to the PD state and progression.

New Avenues for Parkinson’s Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota

“…More recently, one study investigated the effects of intraduodenal infusion of levodopa-carbidopa intestinal gel (LCIG) compared to L-dopa administration in gut microbiota composition. Interestingly, LCIG was related with an increased relative abundance of the Enterobacteriaceae family and the genus Escherichia and Serratia compared with the L-dopa group [ 268 ], suggesting that the pharmacological treatment used influences the gut microbiota composition of PD patients.…”

Parkinson’s Disease: A Prionopathy?

“…Furthermore, pioneering and ongoing human studies have correlated the alteration in the composition of gut microbiota with PD [ 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ]. Although a general agreement on which microbial species are mainly involved has not yet been reached, the most relevant dysbiotic pattern in patients with PD is characterized by a shift in relative bacterial abundances with a prevalence of pathobionts belonging to the phylum Proteobacteria and to the Enterobacteriaceae family [ 117 , 119 , 120 , 123 ].…”

Gut Microbiota Markers and Dietary Habits Associated with Extreme Longevity in Healthy Sardinian Centenarians

“…In fact, the ability of eubiosis to contrast inflammation, alterations in intestinal permeability, as well as the decline of both cognitive and bone health, is well known [19]. When in its dysbiotic state, the GM is capable of affecting the homeostatic systems of the individual [20] and has been associated with diseases (and/or their progression), such as pro-inflammatory conditions [21], cardiovascular [22], neurological [23][24][25][26], hepatic [27], autoimmune diseases [28], as well as metabolic disorders, including obesity and metabolic syndrome [29][30][31] and inflammatory bowel diseases (IBD), such as ulcerative colitis and Crohn's disease [32,33]. Moreover, GM composition has shown to be positively modulated by nutritional pattern, particularly by the Mediterranean Diet (MD), rich in fibres and antioxidant compounds [34,35].…”