A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease.
Overview
- Naval Medical Centre, Naval Medical University, Shanghai, China
Abstract
Background: Alzheimer’s disease (AD) develops through complex interactions between the central nervous system and peripheral systems. The microbiota-metabolite-im
Methods: We used a multi-stage, multi-omics strategy to systematically investigate peripheral–central interactions in AD. The analytical framework integrated Mendelian randomization (MR), summary-data-based Mendelian randomization (SMR), differential expression analysis, machine learning, single-cell and spatial transcriptomics, and quantitative real-time polymerase chain reaction (qPCR) trend confirmation.
Results: Exploratory MR analyses identified multiple microbial taxa, metabolites, and immune cell phenotypes showing associations consistent with potential causal effects on AD. Integrating the SMR and MR findings with differential expression analysis led to the identification of 31 core genetically associated genes. A five-gene predictive model comprising ATF7IP2, TWSG1, PTPRN2, ASCC3 and IGF1R was then developed using machine learning. The diagnostic potential of the individual feature genes was further evaluated in an external validation dataset. Spatial transcriptomic analyses revealed clear cell type-specific expression patterns in brain tissue, with IGF1R, ASCC3and TWSG1 showing potential co-localization in oligodendrocytes. qPCR trend confirmation in pooled samples produced expression trends consistent with the directions inferred from eQTL-based MR.
Conclusions: This study mapped a regulatory network underlying the AD microbiota–metabolite-im
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE36980 — at NCBI GEO; found in the text, “Data sources”
Other data links
- ncbi.nlm.nih.gov/
geo — NCBI; found in the text, “Data sources”
Data availability statement
The original contributions presented in the study are included in the article/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 3 authors, 5 keywords, 9 MeSH terms, 45 references.
Cite
This paper
Wang, B., Yan, W., & Zhang, Y. (2026). A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease. Frontiers in immunology, 17, 1842398. https://
BibTeX
@article{wang2026multi,
author = {Wang, Bei and Yan, Wei and Zhang, Yusheng},
title = {{A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease}},
journal = {Frontiers in immunology},
year = {2026},
month = jul,
volume = {17},
pages = {1842398},
publisher = {Frontiers Media SA},
issn = {1664-3224},
doi = {10.3389/
url = {https://
pmid = {42519311},
pmcid = {PMC13381253}
}
RIS
TY - JOUR
AU - Wang, Bei
AU - Yan, Wei
AU - Zhang, Yusheng
TI - A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease
T2 - Frontiers in immunology
J2 - Front Immunol
PY - 2026
DA - 2026/
VL - 17
SP - 1842398
SN - 1664-3224
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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"page": "1842398",
"DOI": "10.3389/
"PMID": "42519311",
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"ISSN": "1664-3224",
"publisher": "Frontiers Media SA",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
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