Evidence map›Paper›PMID 42533069›Full record

ArticleNature microbiology2026

Microbiota-derived 10-hydroxystearic acid activates PPARα to restore gut epithelial barrier integrity and enhance anti-retroviral therapy.

Dylan Kramer, Clarissa Santos Rocha, Christopher A Gaulke, Marie Nearing, Sumathi Sankaran-Walters, Ikaika Loque, Anugraha Kidigannappa, Eric Pham, Shuang Hu, Patrawin Wanakumjorn and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature microbiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Dylan KramerDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Clarissa Santos RochaDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Christopher A GaulkeDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois Urbana-Champaign, Champaign, IL, USA.
Marie NearingDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Sumathi Sankaran-WaltersDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Ikaika LoqueDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.ORCID http://orcid.org/0009-0008-3354-190X
Anugraha KidigannappaDepartment of Materials Science and Engineering, University of California Davis, Davis, CA, USA.
Eric PhamDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.ORCID http://orcid.org/0009-0005-9320-3601
Shuang HuDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Patrawin WanakumjornDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.ORCID http://orcid.org/0009-0005-4757-0566
Ramona AbbattistaDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.
Abhaya DandekarDepartment of Plant Sciences, University of California Davis, Davis, CA, USA.ORCID http://orcid.org/0000-0001-7925-4086
Roland FallerDepartment of Chemical Engineering, Texas Tech University, Lubbock, TX, USA.ORCID http://orcid.org/0000-0001-9946-3846
Satya DandekarDepartment of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA. sdandekar@health.ucdavis.edu.ORCID http://orcid.org/0000-0002-6346-8028

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
"Corral and Kill" strategy for HIV eradication using MSC in an SIV modelR37AI153025 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Satya Dandekar · 2020 to 2026
$5.3M
Early HIV Effects on Gut Immunity and Inflammation for Seeding Viral ReservoirsR01AI123105 · NIAID · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DANDEKAR, SATYA · 2016 to 2020
$3.8M
Animal Models of Infectious Diseases Training ProgramT32AI060555 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI MCSORLEY, STEPHEN J · 2004 to 2025
$3.3M
Defining the impact of developmental herbicide exposures on gut microbiome physiology and interactions with healthR01ES036174 · NIEHS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Christopher A Gaulke · 2025 to 2026
$1.3M
NIAID NIH HHS R01 AI123105NIAID NIH HHS R37 AI153025NIAID NIH HHS T32 AI060555NIEHS NIH HHS R01 ES036174NIH HHS P51 OD011107ODCDC CDC HHS P51 OD011107U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI123105U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) R37 AI 153025
6 · The paper itself

Abstract

HIV infection disrupts gut epithelial barrier integrity and mucosal immunity, driving chronic inflammation and disease progression which are not fully resolved despite anti-retroviral therapy. Here we identify the microbiota-derived octadecanoid-hydroxy-fatty-acid metabolite 10-hydroxystearic acid (10-HSA), produced by Lactiplantibacillus plantarum, as a key mediator of gut epithelial barrier repair in human intestinal epithelial cells in vitro, ex vivo and in the non-human primate model of HIV/AIDS. X-ray crystallography and transcriptomics combined with functional analyses revealed that 10-HSA directly binds PPARα, inducing lipid metabolism, mitochondrial regeneration and subsequent epigenetic histone crotonylation, thereby promoting gut epithelial renewal. Co-administration of 10-HSA with anti-retroviral therapy in SIV-infected macaques accelerated viral suppression, resolved systemic inflammation, repaired gut epithelial integrity and recovered the gut microbiota. These findings identify a microbiota-derived lipid metabolite-PPARα-histone crotonylation axis that activates gut epithelial regeneration. This study defines a host-microbiome metabolic pathway that restores epithelial-immune homeostasis and enhances the efficacy of anti-retroviral therapy.

Indexed as

Anti-Retroviral AgentsGastrointestinal MicrobiomeIntestinal MucosaPPAR alphaAnimalsDisease Models, AnimalEpithelial CellsHIV InfectionsHumansIntestinal Barrier FunctionLipid MetabolismMacaca mulattaSimian Immunodeficiency VirusAnti-Retroviral AgentsPPAR alpha

Identifiers

PMID42533069
PMCPMC13423806

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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.