Does Gut Microbiota Influence the Course of Parkinson’s Disease? A 3-Year Prospective Exploratory Study in de novo Patients

Article type: Research Article

Authors: Cilia, Roberto^{a; 1; 2; *} | Piatti, Marco^{b; 2} | Cereda, Emanuele^{c; 2} | Bolliri, Carlotta^d | Caronni, Serena^d | Ferri, Valentina^d | Cassani, Erica^d | Bonvegna, Salvatore^{a; 1} | Ferrarese, Carlo^b | Zecchinelli, Anna L.^d | Barichella, Michela^{d; 3} | Pezzoli, Gianni^{d; e; 3}

Affiliations: [a] Fondazione IRCCS Istituto Neurologico Carlo Besta, Parkinson and Movement Disorders Unit, Milan, Italy | [b] Department of Neurology, Milan Center for Neuroscience, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy | [c] Clinical Nutrition and Dietetics Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy | [d] Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy | [e] Fondazione Grigioni per il Morbo di Parkinson, Milan, Italy

Correspondence: [*] Correspondence to: Roberto Cilia, MD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Movement Disorders Unit, via Celoria 11, 20133, Milan, Italy. Tel.: +39 23942368; Fax: +39 23942539; E-mail: [email protected].

Note: [1] Previous affiliation: Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy

Note: [2] These authors contributed equally to this work

Note: [3] These authors shared senior authorship

Abstract: Background:Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson’s disease (PD), prospective studies on de novo patients are lacking. Objective:To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period. Methods:16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients. Multiple confounders were taken into account, including dietary habits. Motor and non-motor symptoms were assessed using validated scales at baseline and followed-up yearly for 3 years. At last follow-up, a detailed neuropsychological assessment was additionally performed. A general linear model for repeated measurements— adjusted by dopaminergic therapy at follow-up— was used to investigate the relationship between bacterial taxa abundance at baseline (stratified by the median of distribution at baseline) and outcome variables. Results:Twenty-five patients were included (11 refused, 2 lost at follow-up, 1 died). Lower abundance of Roseburia (Firmicutes phylum) at baseline was associated with worse evolution of motor, non-motor and cognitive functions at 3-year follow-up. Similarly, lower abundance of Ruminococcaceae and Actinobacteria at baseline was associated with faster worsening of global cognitive functions. At follow-up, frontal lobe functions were the features most robustly associated with baseline microbial abnormalities. Conclusion:In the present exploratory study on de novo PD, we found an association between abnormal distribution of specific bacterial taxa and the progression of motor and non-motor features over a 3-year period. This proof-of-principle study supports the design of a larger observational study aiming to determine whether these differences survive multiple-comparison correction and define microbiota-specific subgroups suitable for therapeutic targeting.

Keywords: Parkinson’s disease, de novo, gut microbiota, prospective study, prognosis

DOI: 10.3233/JPD-202297

Journal: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2020