Parkinson’s disease and the gastrointestinal microbiome

Abstract

Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM and Parkinson's disease (PD) and the realisation that the GM can act via a complex bidirectional communication between the gut and the brain. Compelling evidence suggests that a shift in GM composition may play an important role in the pathogenesis of PD by facilitating the characteristic ascending neurodegenerative spread of αsynuclein aggregates from the enteric nervous system to the brain. Here, we review evidence linking GM changes with PD, highlighting mechanisms supportive of pathological α-synuclein spread and intestinal inflammation in PD. We summarise existing patterns and correlations seen in clinical studies of the GM in PD, together with the impacts of non-motor symptoms, medications, lifestyle, diet and aging on the GM. Roles of GM modulating therapies, including probiotics and faecal microbiota transplantation are discussed. Encouragingly, alterations in the GM have repeatedly been observed in PD, supporting a biological link and highlighting it as a potential therapeutic target.

Changes in Gastrointestinal Microbiome Composition in PD: A Pivotal Role of Covariates

“…Delineating the influence of the collection method and the rRNA sequencing approach on microbiome composition in PD would give important insights for planning of future trials on microbiota composition in PD. Despite these methodological differences, two recent reviews suggest an increasing comparability of microbiota composition across studies (14,17). In addition to sample collection and sequencing, in particular statistical methods used to analyze microbiome data have a profound impact.…”

“…Also, it is currently not well-understood how disease duration and stage, and motor impairment affect microbiota composition in PD. Summaries of observed changes and the methods used in previous studies have been published, recently (14,17). While dysbiosis has been shown in all studies, a consistent picture of a "PD specific microbiome composition" is debatable.…”

What Have We Learned from Cerebrospinal Fluid Studies about Biomarkers for Detecting LRRK2 Parkinson’s Disease Patients and Healthy Subjects with Parkinson’s-Associated LRRK2 Mutations?

“…Inflammatory changes including microglial activation [150,151], increased levels of pro-inflammatory cytokines [152], and complement activation [153,154] are present in the PD brain. There is also evidence for peripheral inflammation in PD [155,156] including in the gastrointestinal system [157], where changes in gut microflora (the "gastrointestinal microbiome") have been suggested to contribute to PD's pathogenesis [158]. LRRK2 has been suggested to be a regulator of inflammation [159].…”

The Effects of COVID-19 and Quarantine Measures on the Lifestyles and Mental Health of People Over 60 at Increased Risk of Dementia

“…The SARS-CoV-2 virus which causes COVID-19 may affect central and peripheral nervous system ( 3 , 4 ), having potential effects on the development and progression of neurodegenerative diseases ( 5 ). SARS-CoV-2 may also affect the cells of the intestinal mucosa, triggering intestinal inflammation and dysbiosis and potentially causing short and long-term alterations of gut microbiota, which have demonstrated strong associations with, neuroinflammation and neurodegenerative diseases ( 6 , 7 ).…”