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 (Naive-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 Naive-Group, the univariate analysis showed a reduction of Blautia, Lachnospirae in LD-Group. Moreover, an 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.

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

Fabbri, Margherita;Sarchioto, Marianna;Zibetti, Maurizio;Lopiano, Leonardo;Serra, Alessandra;
2021

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 (Naive-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 Naive-Group, the univariate analysis showed a reduction of Blautia, Lachnospirae in LD-Group. Moreover, an 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.
28
4
1198
1209
Duodopa; LCIG; Levodopa; Parkinson; microbiota
Melis, Marta; Vascellari, Sarah; Santoru, Maria Laura; Oppo, Valentina; Fabbri, Margherita; Sarchioto, Marianna; Murgia, Daniela; Zibetti, Maurizio; Lopiano, Leonardo; Serra, Alessandra; Palmas, Vanessa; Pisanu, Silvia; Perra, Daniela; Madau, Veronica; Cusano, Roberto; Uva, Paolo; Mereu, Alessandra; Contu, Paolo; Morelli, Micaela; Atzori, Luigi; Melis, Maurizio; Manzin, Aldo; Cossu, Giovanni
File in questo prodotto:
File Dimensione Formato  
MELIS.pdf

Accesso aperto con embargo fino al 13/11/2021

Tipo di file: POSTPRINT (VERSIONE FINALE DELL’AUTORE)
Dimensione 3.09 MB
Formato Adobe PDF
3.09 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1763205
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 9
social impact