Evidence map›Paper›PMID 34854884›Full record

ArticleThe Journal of experimental medicine2022

Gut microbiota-driven brain Aβ amyloidosis in mice requires microglia.

Hemraj B Dodiya, Holly L Lutz, Ian Q Weigle, Priyam Patel, Julia Michalkiewicz, Carlos J Roman-Santiago, Can Martin Zhang, Yingxia Liang, Abhinav Srinath, Xulun Zhang and 8 more

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 2 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

79 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  20. Microbiology spectrum · 2025
    Article

19 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

18 authors.

Hemraj B DodiyaDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-0908-0014
Holly L Lutz *Department of Pediatrics and Scripps Institution of Oceanography, University of California, San Diego, San Diego, CA.ORCID 0000-0001-6454-809X
Ian Q Weigle *Department of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-1904-4367
Priyam PatelCenter for Genetic Medicine, Northwestern University, Chicago, IL.ORCID 0000-0002-9433-5017
Julia MichalkiewiczDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0003-2651-0642
Carlos J Roman-SantiagoDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-1414-7359
Can Martin ZhangDepartment of Neurology, Harvard Medical School, Boston, MA.ORCID 0000-0002-4340-5118
Yingxia LiangDepartment of Neurology, Harvard Medical School, Boston, MA.ORCID 0000-0003-3090-5815
Abhinav SrinathDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0001-7336-7231
Xulun ZhangDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-1023-3014
Jessica XiaDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-1033-2055
Monica OlszewskiDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0001-6220-789X
Xiaoqiong ZhangDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-4978-100X
Matthew John SchipmaCenter for Genetic Medicine, Northwestern University, Chicago, IL.ORCID 0000-0002-0865-1057
Eugene B ChangDepartment of Digestive Diseases, The University of Chicago, Chicago, IL.ORCID 0000-0001-5972-8248
Rudolph E TanziDepartment of Neurology, Harvard Medical School, Boston, MA.ORCID 0000-0002-7032-1454
Jack A GilbertDepartment of Pediatrics and Scripps Institution of Oceanography, University of California, San Diego, San Diego, CA.ORCID 0000-0001-7920-7001
Sangram S SisodiaDepartment of Neurobiology, The University of Chicago, Chicago, IL.ORCID 0000-0002-4039-8864

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI LIU, CAMBRIAN YANGSHAO · 1990 to 2025
$29.8M
Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)T32HD007009 · NICHD · UNIVERSITY OF CHICAGO · PI NANCY B SCHWARTZ · 1985 to 2026
$13.0M
UNIVERSITY OF CHICAGO PREPR25GM066522 · NIGMS · UNIVERSITY OF CHICAGO · PI CARRILLO, ROBERT ARNULFO, RANDALL, GLENN C · 2004 to 2024
$6.7M
Alzheimer's AssociationNICHD NIH HHS T32 HD007009NIDDK NIH HHS P30 DK042086NIGMS NIH HHS R25 GM066522
6 · The paper itself

Abstract

We previously demonstrated that lifelong antibiotic (ABX) perturbations of the gut microbiome in male APPPS1-21 mice lead to reductions in amyloid β (Aβ) plaque pathology and altered phenotypes of plaque-associated microglia. Here, we show that a short, 7-d treatment of preweaned male mice with high-dose ABX is associated with reductions of Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes at 9 wk of age in male mice only. More importantly, fecal microbiota transplantation (FMT) from transgenic (Tg) or WT male donors into ABX-treated male mice completely restored Aβ amyloidosis, plaque-localized microglia morphologies, and Aβ-associated degenerative changes. Transcriptomic studies revealed significant differences between vehicle versus ABX-treated male mice and FMT from Tg mice into ABX-treated mice largely restored the transcriptome profiles to that of the Tg donor animals. Finally, colony-stimulating factor 1 receptor (CSF1R) inhibitor-mediated depletion of microglia in ABX-treated male mice failed to reduce cerebral Aβ amyloidosis. Thus, microglia play a critical role in driving gut microbiome-mediated alterations of cerebral Aβ deposition.

Indexed as

Amyloid beta-PeptidesAmyloidosisAnimalsAntibodiesBrainChemokinesCytokinesFecal Microbiota TransplantationFecesFemaleGastrointestinal MicrobiomeGene Expression ProfilingGene OntologyMaleMiceMice, Inbred C57BLAmyloid beta-PeptidesAntibodiesChemokinesCytokines

Identifiers

PMID34854884
PMCPMC8647415

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.