Evidence map›Paper›PMID 41273231›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Fecal short-chain fatty acids vary by sex and amyloid status.

Jessamine F Kuehn, Qijun Zhang, Margo B Heston, Jea Woo Kang, Sandra J Harding, Nancy J Davenport-Sis, Darby C Peter, Robert L Kerby, Vaibhav Vemuganti, Emma C Schiffmann and 24 more

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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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  11. Fecal short-chain fatty acids vary by sex and amyloid status.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

34 authors.

Jessamine F KuehnDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.ORCID 0000-0002-2719-2474
Qijun ZhangDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Margo B HestonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Jea Woo KangWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sandra J HardingWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Nancy J Davenport-SisWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Darby C PeterWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Robert L KerbyDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Vaibhav VemugantiDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Emma C SchiffmannDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Michael M TallonDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Joseph HarptDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Arun HajraDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
J L WheelerWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sushma ShankarWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Alissa MickolWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Justus ZemberiWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Hana ChowWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Eric ZhangWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Eleanor ClementsWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Hanna NoughaniWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Allison ForstWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Grace EverittWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Gwendlyn KollmorgenRoche Diagnostics GmbH, Penzberg, Germany.
Clara Quijano-RubioRoche Diagnostics International Ltd, Rotkreuz, Switzerland.
Bradley T ChristianWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Cynthia M CarlssonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Henrik ZetterbergWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Tyler K UllandWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Federico E ReyDepartment of Bacteriology, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Barbara B BendlinWisconsin Alzheimer's Disease Research Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Funding

Wisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA MethylationR01AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Nathaniel Ark Chin, Sterling C Johnson · 2007 to 2026
$35.6M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Sanjay Asthana · 2019 to 2026
$34.5M
Gut barrier function in Alzheimer's DiseaseR01AG070973 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2021 to 2025
$3.9M
ß-hydroxybutyrate inhibition of pathology in Alzheimer's diseaseR01AG083883 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2023 to 2026
$3.8M
Gut microbiome intervention in preclinical and clinical Alzheimer's diseaseR61AG088913 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin, Federico E Rey · 2025 to 2026
$900k
Exploring the role of Imidazole Propionate on Alzheimer’s Disease and Related DementiasR21AG089348 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA, REY, FEDERICO E · 2024 to 2025
$408k
The Disadvantage Exposome as a Driver of Alzheimer’s Disease PathologyF99NS130922 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI HESTON, MARGO · 2022 to 2022
$48k
an anonymous philanthropist and donorFamiljen Rönströms Stiftelse, Stockholm, SwedenHjärnfonden, SwedenLa Fondation Recherche Alzheimer (FRA), Paris, FranceNational Science Foundation Graduate Research Fellowship Program 2137424NIA NIH HHS P30 AG062715NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG070973NIA NIH HHS R01AG070973NIA NIH HHS R01 AG083883NIA NIH HHS R01AG083883NIA NIH HHS R21 AG089348NIA NIH HHS R21AG089348NIA NIH HHS R61 AG088913NIH/NINDSNINDS NIH HHS F99 NS130922Swedish Alzheimer's FoundationSwedish State Support for Clinical Researchthe ALF-agreementthe Alzheimer's Association 2021 Zenith Awardthe Alzheimer's Association 2022-2025 Grantthe European Union Joint Program for Neurodegenerative Disordersthe European Union's Horizon Europe Research and Innovation Programmethe Graduate School and the Office of the Vice Chancellor for Research, University of Wisconsin-Madisonthe Kirsten and Freddy Johansen Foundation, Copenhagen, Denmarkthe Swedish Research Councilthe Swedish state under the agreement between the Swedish government and the County Councilsthe Wisconsin Alumni Research Foundationthe Wisconsin Alzheimer's Disease Research Centerthe Wisconsin Registry for Alzheimer's PreventionWisconsin Partnership Program grant
6 · The paper itself

Abstract

introductionShort-chain fatty acids (SCFAs), produced by gut microbes, influence Alzheimer's disease (AD) pathology in animals. Less is known about SCFAs and AD in humans. We profiled feces of adults along the AD continuum to investigate gut microbiome and SCFA associations with AD pathology and cognition.

methodsWe measured SCFAs and bacterial abundances in fecal samples from 287 participants in the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention. We performed regressions examining associations between SCFAs or gut microbes and AD pathology and cognition.

resultsFecal propionate, isovalerate, and propionate-producing bacteria are inversely associated with amyloid status. Mediation analysis found that propionate mediates sex-specific associations between SCFAs and cerebrospinal fluid biomarkers. SCFA levels are associated with slower cognitive decline. DISCUSSION: These results link SCFAs and propionate-producing bacteria with AD. This may inform efforts to leverage diet and specific bacteria to boost SCFA production and potentially ameliorate AD progression. HIGHLIGHTS: Fecal SCFAs link to lower amyloid burden and microglial activation, notably in females. SCFA-producing gut microbes have reduced abundance in amyloid-positive participants. Fecal propionate mediates relationships between gut microbes and amyloid status. SCFAs are associated with slower plasma pTau

Indexed as

Alzheimer DiseaseFatty Acids, VolatileFecesGastrointestinal MicrobiomeAgedBiomarkersCognitive DysfunctionFemaleHumansMaleSex FactorsBiomarkersFatty Acids, VolatileAlzheimer's diseaseamyloidbacteriacerebrospinal fluid biomarkersgut microbiomemetabolitesmicrobiotashort‐chain fatty acids

Identifiers

PMID41273231
PMCPMC12639406

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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.