Beyond bacteria: a multi-omics view of the gut–brain axis in Parkinson’s disease

Overview

1. Department of Mathematics, University of Maryland, College Park, MD, United States
2. Winston Churchill High School, Potomac, MD, United States
3. Department of Epidemiology and Biostatistics, University of Maryland, College Park, MD, United States
4. Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, United States

Abstract

Introduction: Parkinson's disease (PD) is increasingly recognized as a multisystem disorder in which gastrointestinal dysfunction and gut microbial alterations may contribute to disease pathophysiology. Although most microbiome research in PD has focused on bacteria, growing evidence suggests that the gut ecosystem should be considered more broadly to include fungi, viruses, metabolites, and proteins.

Methods: We searched PubMed and SciFinder for human studies published up to October 28, 2025, using domain-specific search strategies for the bacteriome, metabolome, proteome, virome, and mycobiome, and synthesized the eligible evidence using a structured multi-omics evidence-mapping framework.

Results: We summarize the most consistent bacterial findings, including enrichment of mucin-degrading taxa and depletion of short-chain fatty acid-producing commensals, and discuss how these changes relate to impaired fermentation, barrier dysfunction, and immune activation. We further examine emerging evidence for virome and mycobiome alterations, highlighting the possibility that PD-related dysbiosis reflects cross-kingdom ecological disruption rather than bacteria-only imbalance. Metabolomic studies provide functional support for this model by demonstrating altered short-chain fatty acid biology and broader host -microbe co-metabolic remodeling. Protein-focused studies, including host proteomic signatures and bacterial functional amyloids, extend the field toward mechanisms linking gut dysfunction to inflammation, proteostatic stress, and α-synuclein pathology.

Discussion: Overall, the evidence supports a multi-layer view of the PD gut -brain axis in which microbial ecology, metabolic output, barrier integrity, immune signaling, and protein-centered mechanisms are interconnected. The field remains limited by cross-sectional designs, methodological heterogeneity, and uneven evidence depth across omics layers. Longitudinal, standardized, and integrated multi-omics studies will be essential to determine which microbiome-associated alterations are mechanistically important, clinically informative, and potentially modifiable in PD.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

No dataset and no data link were found in the paper.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material; the full list of included studies is provided in Supplementary Table 2. Code and publication-ready files for the figures are available in the public GitHub repository at https://github.com/hanhuiyeye/PD. An R Shiny application that generates PRISMA 2020 flow diagrams, developed alongside this review, is deployed at https://eok7.shinyapps.io/PRISMA/ (source code: https://github.com/euniceokk/prisma). Further inquiries can be directed to the corresponding author.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 8 authors, 8 keywords, 60 references.

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This paper

Han, H., Luo, O., Li, K., Rahaman, S., Ok, E. U., Zhang, L., Liang, M., & Lin, H. (2026). Beyond bacteria: a multi-omics view of the gut–brain axis in Parkinson’s disease. Frontiers in cellular and infection microbiology, 16, 1900578.

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