The Role of the Microbiome Across Neurological and Neurodegenerative Disorders: A Quantitative Systematic Review
Emily Song1, Sam Degregori2, Harrison Gu4, Isabella Huang4, David Kobobel4, Rob Knight3
1Department of Biomedical Engineering, Duke University, 2Department of Pediatrics, 3Departments of Pediatrics, Bioengineering, and Computer Science & Engineering, University of California San Diego, 4Department of Biology, Johns Hopkins University
Objective:
Evaluate clinical associations between microbiome features and neurological disorders and test whether directional taxonomic shifts are consistent within and across diseases, emphasizing Alzheimer’s disease (AD) and Parkinson’s disease (PD).
Background:
The human microbiome influences metabolism, immunity, and brain health. Dysbiosis has been linked to neurologic conditions, but the consistency of clinical associations and taxon-level enrichment or depletion across diseases remains unclear.
Design/Methods:
We conducted an umbrella review of 63 studies (past 10 years; PRISMA). From each study we extracted specimen site, sequencing modality (16S/shotgun), design, diversity metrics, reported taxa and their enrichment or depletion relative to control, and clinical scales. Clinical-association was coded (Yes/No/Not Reported) if a statistically significant association between a microbiome measure and clinical phenotype was described. We performed a vote-count synthesis: for each (taxon, disease) we tallied enrichment and depletion, computed net effect and support (total studies), and compared bins with Fisher’s exact tests. Prespecified bins captured canonical short-chain fatty acid (SCFA) producers.
Results:
Clinical associations were reported in 40/44 evaluable (90.9%) studies. Across disorders, SCFA-producing taxa (e.g., Faecalibacterium, Roseburia, Blautia, Agathobacter, Eubacterium, Butyricicoccus, Ruminococcus) were significantly more often depleted than enriched (2×2 table [[39 pos, 24 neg] vs [11 pos, 52 neg]]; OR = 7.68, p = 5.3×10⁻⁷). Disease-specific patterns mirrored this signature: PD: recurrent depletion of SCFA-linked taxa (Faecalibacterium, Roseburia, Blautia) with enrichment of other genera (e.g., Akkermansia, Desulfovibrio, Escherichia). AD: frequent depletion of SCFA taxa (Faecalibacterium, Eubacterium, Roseburia), with variable enrichment of Bacteroides, Akkermansia, and Prevotella. Signals spanned multiple sites and methods, with heterogeneity and stage-specific effects (e.g., preclinical AD).
Conclusions:
A reproducible cross-disease signature of SCFA-producer depletion accompanies neurological disorders and co-varies with clinical scales. This evidence synthesis clarifies within-disease consistency versus mixed findings—particularly in AD and PD—and supports the need for standardized, longitudinal, multi-omics studies to refine causality and enable robust diagnostic biomarkers.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.