Evidence map›Paper›PMID 35017199›Full record

ArticleGut2022

Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation.

Chun Chen, Jianming Liao, Yiyuan Xia, Xia Liu, Rheinallt Jones, John Haran, Beth McCormick, Timothy Robert Sampson, Ashfaqul Alam, Keqiang Ye

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
289citing papers in PubMed, 6 pooled it
34.7field-weighted citation impact, top 1% of its field
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

289 citing papers in PubMed, 6 syntheses or guidelines pooled it, 418 citations in OpenAlex.

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229 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 2 countries.

Chun Chen *Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.ORCID 0000-0003-3041-3263
Jianming Liao *Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Yiyuan XiaDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Xia LiuDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA.
Rheinallt JonesDepartment of Pediatrics, Emory University, Atlanta, Georgia, USA.ORCID 0000-0002-0415-9487
John HaranDepartment of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Beth McCormickDepartment of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Timothy Robert SampsonDepartment of Physiology, Emory University, Atlanta, Georgia, USA.
Ashfaqul AlamMicrobiology, Immunology & Molecular Genetics, University of Kentucky, Lexington, Kentucky, USA.
Keqiang YeDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, USA kq.ye@siat.ac.cn.
Emory University · USUniversity of Massachusetts Chan Medical School · USUniversity of Kentucky · US

Funding

Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1M
The Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Amy D Rodriguez · 2020 to 2026
$29.0M
Understanding the role of anti-apolipoprotein A-I antibodies in atherosclerotic cardiovascular diseaseP20GM130456 · NIGMS · UNIVERSITY OF KENTUCKY · PI Lindsay Christine Czuba · 2020 to 2026
$18.7M
Understanding the Microbiome-gut-brain axisn Alzheimer disease and its Role in Cognitive DeclineRF1AG067483 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HARAN, JOHN PATRICK · 2020 to 2020
$3.3M
ApoE4 and C/EBP: Mutually Regulate Each Other in Alzheimer's DiseaseR01AG065177 · NIA · EMORY UNIVERSITY · PI BENIAN, GUY MARTIN · 2020 to 2024
$2.3M
The elderly gut microbiome during transition to long-term care and the risk of Clostridium difficile carriageK23AG057790 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI HARAN, JOHN PATRICK · 2018 to 2021
$757k
Microbially generated protons mediate interkingdom host-microbiome cross-talk and maintain intestinal homeostasis via reciprocal functions of two proton-sensing GPCRsK01DK114391 · NIDDK · UNIVERSITY OF KENTUCKY · PI ALAM, M. ASHFAQUL · 2017 to 2021
$530k
Impact of dysbiotic and symbiotic catabolism of luminal amino acids on intestinal epithelial barrier function and inflammationR56DK136728 · NIDDK · UNIVERSITY OF KENTUCKY · PI ALAM, M. ASHFAQUL · 2023 to 2023
$375k
NCATS NIH HHS UL1 TR002378NIA NIH HHS K23 AG057790NIA NIH HHS P30 AG066511NIA NIH HHS R01 AG065177NIA NIH HHS RF1 AG067483NIDDK NIH HHS K01 DK114391NIDDK NIH HHS R56 DK136728NIGMS NIH HHS P20 GM130456
6 · The paper itself

Abstract

objectiveThis study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer's disease (AD) pathogenesis.

designWe analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors.

resultsMicrobial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology in germ-free 3×Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3×Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients' gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors' microbiota transplants.

conclusionsThese findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.

Indexed as

Alzheimer DiseaseGastrointestinal MicrobiomeInsulinsAnimalsCognitionDisease Models, AnimalDysbiosisFatty Acids, UnsaturatedHumansInflammationInsulin-Like Growth Factor IMiceNeuroinflammatory DiseasesPlaque, AmyloidRNA, Ribosomal, 16SFatty Acids, UnsaturatedInsulin-Like Growth Factor IInsulinsRNA, Ribosomal, 16Sbrain/gut interaction

Identifiers

PMID35017199
PMCPMC10720732
OpenAlexW4205897663

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.