Evidence map›Paper›PMID 41163121›Full record

ArticleBiomarker research2025

Immune, blood-brain barrier, and metabolic biomarkers mediate gut-brain axis crosstalk in alzheimer's disease.

Jincheng Li, Ziyu Yuan, Jialin Li, Zhenqiu Liu, Yingzhe Wang, Mei Cui, Chen Suo, Li Jin, Ding Ding, Xingdong Chen and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Jincheng Li *State Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China.
Ziyu Yuan *Fudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China.
Jialin LiState Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China.
Zhenqiu LiuState Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China.
Yingzhe WangDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Mei CuiDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Chen SuoFudan University Taizhou Institute of Health Sciences, Taizhou, 225300, Jiangsu, China.
Li JinState Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China.
Ding DingInstitute of Neurology, National Clinical Research Center for Aging and Medicine, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Xingdong ChenState Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China. xingdongchen@fudan.edu.cn.
Yanfeng JiangState Key Laboratory of Genetics and Development of Complex Phenotypes, Human Phenome Institute, Research and Innovation Center, Shanghai Pudong Hospital, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200433, China. yanfengjiang@fudan.edu.cn.

Funding

National Natural Science Foundation of China 82373658Natural Science Foundation of Shanghai 22ZR1405300Science and Technology Innovation 2030 Major Projects 2022ZD0211600the National Key R&D Program of China 2023YFC3606300the National Key R&D Program of China 2024YFC3405800
6 · The paper itself

Abstract

backgroundGut microbiota may influence Alzheimer's disease (AD) pathogenesis by modulating host homeostasis. However, population-based causal evidence linking gut dysbiosis to Alzheimer's disease pathogenesis, especially via immune, vascular, and metabolic pathways, remains insufficient.

methodsWe performed Mendelian randomization (MR) and colocalization analysis on 629 gut microbiota features and 2,103 immune, blood-brain barrier (BBB), and metabolic biomarkers regarding the risk of AD and cerebrospinal fluid (CSF) pathological biomarkers.

resultsWe identified that mucin-degraders, short-chain fatty acid (SCFA) producers, and Programmed Cell Death Protein 1/Programmed Death-Ligand 1 (PD-1/PD-L1)-related biomarkers were associated with lower AD risk, while cardiovascular microbes, Amyloid-beta (Aβ)-related proteins, and lipoproteins were linked to higher risk. Increased AD risk was associated with decreased SCFA producers, branched-chain amino acids (BCAAs), and lactate, but with increased liver-disease microbes, fatty acids, and glycoprotein acetyls. Notably, Desulfovibrionaceae and Methanobrevibacter emerged as critical contributors to AD. Erysipelotrichaceae abundance inversely modulates CSF phosphorylated tau (p-tau) pathology while being increased by Aβ42 pathology, suggesting a microbiota-mediated feedback circuit in AD. Mediation analysis highlighted the role of CD28

conclusionsOur study reveals a bidirectional gut-brain feedback loop in AD, in which gut microbiota promote neuroinflammation and immune aging, while AD exacerbates gut dysbiosis via lipid metabolic dysregulation. This self-reinforcing mechanism involving immune signaling, BBB disruption, and SCFA imbalance offers potential targets for integrated microbiota-based interventions in AD prevention.

Indexed as

Alzheimer’s diseaseCirculating Immune–Blood–Brain Barrier–Metabolic biomarkersGut–Brain axisGut microbiotaMendelian randomization

Identifiers

PMID41163121
PMCPMC12573957

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.