Gut microbiome dysbiosis, short-chain fatty acid depletion and implications for neuroinflammation in atypical parkinsonian syndromes – a systematic review of patient cohorts

Introduction Atypical parkinsonian syndromes (APS) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) pose a major clinical challenge due to their progressive disease course, reduced life expectancy and resistance to dopaminergic therapy. The gut microbiome has gained increasing attention as a potential contributor to APS etiology and progression. Aim The literature analysis aims to systematically evaluate alterations in the gut microbiome in APS, their correlation with clinical symptoms and their potential diagnostic and therapeutic relevance. Material and methods PubMed and Web of Science were searched separately for ‘’progressive supranuclear palsy’’, ‘’multiple system atrophy’’ and ‘’corticobasal syndrome’’, each combined with “gut microbiome” AND “human”. Inclusion criteria were ≥ 10 subjects per group, clinically confirmed APS and gut microbiome analysis in a case-control, cross-sectional, longitudinal or randomized controlled trial study design. 7 studies met the inclusion criteria (1 PSP, 1 PSP/MSA, 5 MSA). No studies with CBS patients could be included. Results The gut microbiome is altered in APS compared to healthy controls, with several alterations correlating with clinical symptoms in individual studies. A reduction of short-chain fatty acid (SCFA) producing bacteria and an enrichment of pro-inflammatory taxa were observed, alongside impaired markers of intestinal barrier integrity. Discussion and conclusion APS are associated with dysbiosis that correlates with clinical symptoms, although causality remains to be established. Generalizability is limited due to the lack of geographic heterogeneity in the included studies. Longitudinal studies with larger cohorts are required to identify robust microbial markers and therapeutic potential.