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Alterations in gut microbiota and plasma metabolites: a multi-omics study of mild cognitive impairment in Parkinson’s disease
Zihao Lin, Yangdanyu Li, Yuning Liu, Bo Yang, Peixiao Yin, Chenyang Guan, Yating Fang, Liying Yang et al.. Frontiers in Neuroscience, 2025-12-01
Topic: Brain proteins, microglia and lab models
Introduction Emerging evidence suggests that gut microbiota and plasma metabolites may be associated with the onset and progression of Parkinson’s disease (PD). Results PD patients with mild cognitive impairment (PD-MCI) exhibited distinct microbial and metabolic profiles compared to PD patients with normal cognition (PD-NC). Consistent with both the Gut Microbiota Health Index (GMHI) and Gut Microbiota Health Index (MDI), PD-MCI patients exhibited significant gut microbial dysbiosis. Metabolite analysis revealed that phenylalanine metabolism (including phenylacetylglutamine, 2-hydroxycinnamic acid, N-acetyl-L-phenylalanine, and phenylacetylglycine) and PPAR signaling pathways (including 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid) were downregulated in the PD-MCI group, while choline metabolism in cancer (including PC(18:1(11Z)/18:3(6Z,9Z,12Z)) and LysoPC(18:3(6Z,9Z,12Z)/0:0)) was upregulated. Notably, phenylacetylglutamine demonstrated robust diagnostic potential (AUC = 0.8222), emerging as a promising biomarker for PD-MCI. Correlation analysis revealed significant associations between key microbial taxa (particularly g__Eggerthella and SCFA-producing genera) and metabolites (phenylacetylglutamine, and uridine 2′,3′-cyclic phosphate), suggesting their interactive role in PD cognitive impairment through gut-brain axis mechanisms. Conclusion Our multi-omics study revealed distinct gut microbiota and metabolite alterations in PD patients with cognitive impairment, highlighting gut-brain axis dysfunction. Key microbial and metabolic markers demonstrated diagnostic potential, providing new insights into the pathophysiology of PD-related cognitive decline and potential targets for future therapeutic strategies.
Key findings
- Introduction Emerging evidence suggests that gut microbiota and plasma metabolites may be associated with the onset and progression of Parkinson’s disease (PD).
- Results PD patients with mild cognitive impairment (PD-MCI) exhibited distinct microbial and metabolic profiles compared to PD patients with normal cognition (PD-NC).
- Consistent with both the Gut Microbiota Health Index (GMHI) and Gut Microbiota Health Index (MDI), PD-MCI patients exhibited significant gut microbial dysbiosis.
- Metabolite analysis revealed that phenylalanine metabolism (including phenylacetylglutamine, 2-hydroxycinnamic acid, N-acetyl-L-phenylalanine, and phenylacetylglycine) and PPAR signaling pathways (including 8-hydroxy-5Z,9E,11Z,14Z-eicosatetraenoic acid) were downregulated in the PD-MCI group, while choline metabolism in cancer (including PC(18:1(11Z)/18:3(6Z,9Z,12Z)) and LysoPC(18:3(6Z,9Z,12Z)/0:0)) was upregulated.
- Notably, phenylacetylglutamine demonstrated robust diagnostic potential (AUC = 0.8222), emerging as a promising biomarker for PD-MCI.
Why it matters
This multi-omics study found that Parkinson's disease patients with mild cognitive impairment had distinct gut microbial and metabolic profiles compared with those with normal cognition. It identifies phenylacetylglutamine as a promising biomarker for Parkinson's disease mild cognitive impairment, which is about diagnosis rather than treating or preventing Alzheimer's.
Study details
- Participants100
- Effect sizeAUC = 0.8222
- Evidence strengthModerate
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in Neuroscience) |
| Journal's citation record | 2 / 4 | Frontiers in Neuroscience: journal h-index 226 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 100 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 0 / 4 | Last-listed author Chuanying Xu: h-index 2 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Xuzhou Medical College: institution h-index 242 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41404035) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fnins.2025.1667331
- PubMed: 41404035
- Original source →
- Free full text: Frontiers in Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Lin, Z., Li, Y., Liu, Y., Yang, B., Yin, P., Guan, C., et al. (2025). Alterations in gut microbiota and plasma metabolites: a multi-omics study of mild cognitive impairment in Parkinson’s disease. Frontiers in Neuroscience. https://doi.org/10.3389/fnins.2025.1667331
Vancouver
Lin Z, Li Y, Liu Y, Yang B, Yin P, Guan C, et al. Alterations in gut microbiota and plasma metabolites: a multi-omics study of mild cognitive impairment in Parkinson’s disease. Frontiers in Neuroscience. 2025. doi:10.3389/fnins.2025.1667331. PMID: 41404035.
BibTeX
@article{lin2025-41404035,
author = {Lin, Zihao and Li, Yangdanyu and Liu, Yuning and Yang, Bo and Yin, Peixiao and Guan, Chenyang and Fang, Yating and Yang, Liying and others},
title = {{Alterations in gut microbiota and plasma metabolites: a multi-omics study of mild cognitive impairment in Parkinson’s disease}},
journal = {Frontiers in Neuroscience},
year = {2025},
doi = {10.3389/fnins.2025.1667331},
pmid = {41404035},
url = {https://doi.org/10.3389/fnins.2025.1667331}
}
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