Evidence map›Paper›PMID 40676515›Full record

ArticleBMC neuroscience2025

Post-stroke butyrate treatment shows sex-dependent microglial responses but does not improve outcomes in a mouse model of endothelin-1 sensory motor stroke.

Ashley de Witte, Juliana Montoya Sanchez, Emerson Daniele, Jingan Chen, Yibang Fan, Pranav Khatri, Daniela Lozano Casasbuenas, Angel Zhang, Kathryn G Todd, Maryam Faiz and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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.

Ashley de Witte *Division of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Juliana Montoya Sanchez *Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
Emerson DanieleInstitute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Jingan ChenDivision of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Yibang FanDivision of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Pranav KhatriDivision of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Daniela Lozano CasasbuenasDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Angel ZhangDivision of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada.
Kathryn G ToddNeurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
Maryam Faiz *Division of Anatomy, Department of Surgery, University of Toronto, Toronto, ON, Canada. Maryam.faiz@utoronto.ca.
Matthew Churchward *Neurochemical Research Unit, Department of Psychiatry, University of Alberta, Edmonton, AB, Canada. churchwa@ualberta.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundStroke induces gut dysbiosis and reduces microbial production of short-chain carboxylic acids (SCCAs), which negatively correlates with stroke outcomes. Previous studies have demonstrated that SCCA supplementation can improve functional recovery, with one recent study suggesting this occurs via modulation of microglial responses. However, the effects of individual SCCAs on microglial responses remain unclear, particularly across sexes and following a more clinically relevant, post-stroke treatment protocol. To address this gap, we investigated the effect of post-stroke supplementation with butyrate on stroke outcomes and microglial responses in both male and female mice over time.

resultsPost-stroke butyrate treatment produced sex-specific microglial responses. In females, butyrate increased microglial ramification at chronic timepoints in vivo and enhanced IL6 release following IFNγ stimulation in vitro. These microglial changes were not observed in males. Despite the distinct microglial responses, butyrate treatment did not correlate with improved stroke outcomes in either sex, as measured by lesion volume and functional recovery.

conclusionsOur findings reveal previously unknown sex differences in microglial responses to butyrate following stroke. Despite these microglial changes in females, butyrate treatment did not improve functional outcomes in either sex, suggesting that sex-specific optimization of dosing and delivery may be needed for therapeutic efficacy.

Indexed as

ButyratesMicrogliaSex CharacteristicsStrokeAnimalsDisease Models, AnimalEndothelin-1FemaleMaleMiceMice, Inbred C57BLRecovery of FunctionButyratesEndothelin-1ButyrateGut-brain axisIschemic strokeMicrogliaSex differencesShort-chain carboxylic acids (SCCAs)Short-chain fatty acids (SCFAs)Stroke

Identifiers

PMID40676515
PMCPMC12273294

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LicenceCC BY
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Registered trials

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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.