Gut-brain axis dysfunction in Parkinson's disease: a meta-analysis of microbiome dysbiosis and intestinal barrier...

Parkinson's disease (PD) has traditionally been conceptualized as a neurodegenerative disorder centered within the central nervous system. However, growing evidence suggests that gastrointestinal dysfunction, intestinal permeability abnormalities, and gut microbiome dysbiosis may contribute to disease initiation and progression in a subset of patients. While several studies have characterized microbial alterations in PD, the integration of dysbiosis with intestinal barrier dysfunction and emerging phenotype-oriented models remains incompletely synthesized.

A systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases were searched from inception to January 2025 for studies evaluating gut microbiota composition and/or intestinal permeability markers in Parkinson's disease. Random-effects meta-analysis was performed using standardized mean differences (SMDs) with subgroup and sensitivity analyses exploring geographic variation, sequencing methodology, disease duration, and phenotype-specific findings.

Thirty-four studies were identified; one (an experimental fecal-microbiota-transfer study in mice) was reclassified as preclinical mechanistic evidence rather than a primary human dataset. The remaining 33 human studies comprised 1,588 PD patients and 1,449 healthy controls. Consistent microbial alterations were identified across studies, characterized by depletion of short-chain fatty acid-producing taxa including Prevotellaceae, Faecalibacterium, and Lachnospiraceae, alongside enrichment of Akkermansia, Bifidobacteriaceae, and Christensenellaceae. Elevated fecal calprotectin and zonulin levels suggested concomitant low-grade intestinal inflammation and impaired epithelial barrier integrity. In limited phenotype-stratified subgroup analyses, gut-first PD phenotypes showed potentially more pronounced dysbiosis patterns than brain-first phenotypes; this preliminary observation is based on very few phenotype-stratified studies and requires validation in larger, prospective cohorts. Functional interpretation of the included literature suggested potential alterations in butyrate metabolism, mucosal barrier maintenance, inflammatory signaling, and microbial-host immune interactions.

Parkinson's disease is associated with reproducible alterations in gut microbial composition together with evidence of intestinal barrier dysfunction. Although causality cannot be established from predominantly observational studies, the findings support a biologically plausible role for gut-related mechanisms in disease pathophysiology, with a preliminary signal for more pronounced involvement in gut-first PD phenotypes that remains to be confirmed. Future longitudinal and mechanistic studies integrating microbiome, metabolomic, and permeability data are required to clarify therapeutic and biomarker implications.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251078511, CRD420251078511.