The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism.
Overview
- School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102401, People’s Republic of China
- First Clinical Medical College of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150006, People’s Republic of China
- Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, 100089, People’s Republic of China
Abstract
Objective: This study aimed to identify novel therapeutic targets for Alzheimer’s disease (AD) by investigating the role of the intestinal flora (IF) via the gut-brain axis, and to predict a potential natural compound for AD treatment and elucidate its underlying mechanism.
Methods: Following a primary analytical axis, we first employed Mendelian randomization (MR) to infer causal relationships between gut microbiota and AD. To pinpoint molecular targets, we integrated Summary-data-based MR (SMR) with single-cell and spatial transcriptomics. Subsequently, network pharmacology and molecular docking were used to identify stigmasterol as a candidate compound targeting the causal pathway. Finally, the neuroprotective effects and the STIM1/
Results: MR-based causal inference identified Desulfovibrio as a risk factor for AD, while Slackia and the Lachnospiraceae NK4A136 group were protective factors. Seven key AD-related genes were identified by combining MR results with databases, which were highly druggable. SMR analysis and multi-omics integration pinpointed STIM1-mediated calcium signaling as the core causal pathway. Following the identification of stigmasterol via network pharmacology and molecular docking, in vitro experimental validation confirmed that stigmasterol significantly inhibited Aβ1-42 induced neuronal apoptosis and calcium overload by specifically modulating the STIM1/
Conclusion: This study decodes the gut-brain axis by establishing the specific causal pathway. We demonstrate that Stigmasterol exerts neuroprotective effects by inhibiting apoptosis through a IF-associated mechanism involving the STIM1/
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE175814, at NCBI GEO; found in the text, “Single-Cell RNA Sequencing Data Analysis of…”
Other data links
- ncbi.nlm.nih.gov/
geo , NCBI; found in “Data Sharing Statement”
Data Sharing Statement
The original contributions and experimental data presented in the study are included in the article; further inquiries can be directed to the corresponding author upon reasonable request. The publicly available datasets analyzed in this study can be found in the following repositories: Alzheimer’s disease GWAS data are available from the IEU OpenGWAS project (https://
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 10 authors, 6 keywords, 83 references.
Cite
This paper
Ding, T., Chen, J., Xiang, Y., Zhou, X., Zheng, H., Bai, Y., Wang, W., Fu, Q., Chen, Y., & Fu, Y. (2026). The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism. Degenerative neurological and neuromuscular disease, 16, 580890. https://
BibTeX
@article{ding2026gut,
author = {Ding, Tunan and Chen, Junlei and Xiang, Yunsheng and Zhou, Xiaojie and Zheng, Hongbo and Bai, Yihan and Wang, Weihao and Fu, Qiang and Chen, Yan and Fu, Yin},
title = {{The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism}},
journal = {Degenerative neurological and neuromuscular disease},
year = {2026},
month = apr,
volume = {16},
pages = {580890},
publisher = {Dove Press},
issn = {1179-9900},
doi = {10.2147/
url = {https://
pmid = {42077232},
pmcid = {PMC13135099}
}
RIS
TY - JOUR
AU - Ding, Tunan
AU - Chen, Junlei
AU - Xiang, Yunsheng
AU - Zhou, Xiaojie
AU - Zheng, Hongbo
AU - Bai, Yihan
AU - Wang, Weihao
AU - Fu, Qiang
AU - Chen, Yan
AU - Fu, Yin
TI - The Gut-Brain Axis in Alzheimer's: From Microbiota Genetics to Stigmasterol's Neuroprotection Mechanism
T2 - Degenerative neurological and neuromuscular disease
J2 - Degener Neurol Neuromuscul Dis
PY - 2026
DA - 2026/
VL - 16
SP - 580890
SN - 1179-9900
PB - Dove Press
DO - 10.2147/
UR - https://
LA - en
ER -
CSL-JSON
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