Evidence map›Paper›PMID 42530713›Full record

ArticleMolecular neurobiology2026

Integrative Analysis Reveals Interactions Between Gut Microbiota-Derived Metabolites and the Brain in Parkinson's Disease.

Yiming Shao, Jiaqi Han, Shoukui Hu

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Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

3 authors.

Yiming ShaoCell Research and Translational Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Jiaqi HanDepartment of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Shoukui HuDepartment of Laboratory Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China. shoukuihu@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder increasingly associated with gut microbiota alterations, yet the mechanisms by which microbial metabolites influence PD remain unclear. Here, we applied an integrative computational and experimental strategy to identify key gut microbial metabolites and host genes potentially involved in PD. Differentially abundant gut microbes were obtained from the gutMDisorder database and their corresponding metabolites from gutMGene, with predicted protein targets generated using the Similarity Ensemble Approach. Transcriptomic data from PD brain tissues were analyzed to identify differentially expressed genes, which were intersected with metabolite targets, followed by enrichment and protein-protein interaction analyses. Three machine learning algorithms were applied for gene prioritization, while molecular docking evaluated metabolite-gene binding affinities and ProTox3.0 predicted toxicity and blood-brain barrier permeability. In vitro assays further assessed the functional effects of 3-indolepropionic acid in a rotenone-induced SH-SY5Y cell model. Our analyses identified 44 PD-associated microbial taxa linked to 77 metabolites and 905 predicted target genes, with 29 overlapping differentially expressed genes enriched in synaptic signaling and dopaminergic pathways. Dopamine receptor D2 (DRD2) emerged as a central hub gene, with strong docking interactions predicted for two indole metabolites, 3-(1H-indol-3-yl)propanoate and 3-indolepropionic acid. Functional validation showed that 3-indolepropionic acid improved cell viability, reduced apoptosis, and preserved DRD2 expression under neurotoxic stress. Together, these findings suggest that specific gut microbial metabolites may modulate host dopaminergic signaling via DRD2, offering new insights into the microbiota-brain axis and potential targets for further PD research.

Indexed as

BrainGastrointestinal MicrobiomeParkinson DiseaseCell Line, TumorHumansMolecular Docking SimulationGut–brain axisGut microbiotaIndole compoundsMicrobial metabolitesParkinson’s disease

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.