Evidence mapPaperPMID 41110099Full record

ArticleThe FEBS journal2025

Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages.

Daniela Parada-Venegas, Marjorie De la Fuente López, Karen Dubois-Camacho, Glauben Landskron, Tjasso Blokzijl, Héctor Molina, María-Celeste Casanova, Yingying Cui, Moting Liu, Antonio M Da Costa De Pina and 7 more

Abstract read
In one paragraph

Article in The FEBS journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

17 authors.

Daniela Parada-VenegasDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.ORCID https://orcid.org/0009-0008-0551-5624
Marjorie De la Fuente LópezInnate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Karen Dubois-CamachoDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Glauben LandskronInnate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Tjasso BlokzijlDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Héctor MolinaInnate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
María-Celeste CasanovaInnate Immunity Laboratory, Immunology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Yingying CuiDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Moting LiuDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Antonio M Da Costa De PinaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Daniela SimianGastroenterology Section, Department of Internal Medicine, Hospital Clínico Universidad de Chile José Joaquín Aguirre, Santiago, Chile.
María-Julieta GonzálezCell and Molecular Biology Program, Biomedical Sciences Institute, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Rinse K WeersmaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Rodrigo QueraDigestive Disease Center, Inflammatory Bowel Diseases Program, Clínica Universidad de los Andes, Universidad de los Andes, Santiago, Chile.
Gerard DijkstraDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.
Klaas Nico FaberDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.ORCID https://orcid.org/0000-0001-8893-3312
Marcela A HermosoDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, The Netherlands.ORCID https://orcid.org/0000-0002-7936-7571

Funding

Agencia Nacional de Investigación y Desarrollo 11190990Agencia Nacional de Investigación y Desarrollo 11230904Agencia Nacional de Investigación y Desarrollo 1170648Agencia Nacional de Investigación y Desarrollo 1220702Agencia Nacional de Investigación y Desarrollo 21150517Agencia Nacional de Investigación y Desarrollo 3190931Agencia Nacional de Investigación y Desarrollo 3210367Agencia Nacional de Investigación y Desarrollo ECOS220024Agencia Nacional de Investigación y Desarrollo REDES180134Stichting De Cock-Hadders 2023-09Universidad de Chile PuenteICBM2021_570333University Medical Center Groningen/University of Groningen PhD scholarship
6 · The paper itself

Abstract

Butyrate-producing gut bacteria and luminal butyrate levels are reduced in Inflammatory Bowel Diseases (IBDs). Butyrate has anti-inflammatory properties through mechanisms not well-characterized in IBDs. Here, we determined the butyrate anti-inflammatory effect on primary IBD tissues and intestinal cell models to identify key target cells and pathway(s) involved. Cytokines, monocarboxylate transporter-1 (MCT1), G-protein-coupled receptor-109A (GPR109A), and histone deacetylase-3 (HDAC3) levels were analyzed in IBD and healthy tissues using cytometric bead arrays, RNA-seq analysis and immunofluorescence. Inflammatory markers and phagocytosis in butyrate-treated colonic organoids, primary monocytes or THP-1 macrophages, were assessed by qPCR, flow cytometry and amikacin protection assays, when relevant combined with GPR109A or HDAC3 antagonists. Butyrate suppressed TNF and IL-6 secretion by > 50% in ex vivo-cultured inflamed IBD biopsies. MCT1 expression was reduced in inflamed epithelium and cytokine-exposed organoids, while IL-18 was reduced 0.5-fold in organoids, and both were restored by butyrate, without suppressing pro-inflammatory gene expression. GPR109A and HDAC3 were elevated in IBD tissues and upregulated by butyrate in cultured mucosa. Butyrate also suppressed IL-6, TNF-α, CD40, and CD80 by > 50% and enhanced adherent-invasive Escherichia coli (AIEC) phagocytosis by 62% in monocytes/macrophages. Histone acetylation (H3K9ac) increased > 5-fold, mimicking the HDAC inhibitor SAHA. Contrary, specific GPR109A inhibition and gene G-protein-coupled receptor inhibition did not alter butyrate's effects. Butyrate restores MCT1 and IL-18 gene expression in inflamed epithelial cells, showing limited anti-inflammatory effects. Instead, butyrate targets HDAC3 in mononuclear cells, suppressing inflammation in IBD gut mucosa. The cell-type-specific effects of butyrate offer mechanistic insights that support its therapeutic relevance in IBDs.

Indexed as

ButyratesHistone DeacetylasesInflammatory Bowel DiseasesIntestinal MucosaMacrophagesMonocytesHistone Deacetylase 3Histone Deacetylase InhibitorsHumansInflammationMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersOrganoidsPhagocytosisReceptors, G-Protein-CoupledSymportersButyratesHCAR2 protein, humanHistone Deacetylase 3Histone Deacetylase InhibitorsHistone DeacetylasesMonocarboxylate Transport Protein 1Monocarboxylic Acid TransportersReceptors, G-Protein-CoupledSymportersbutyrateepithelial SLC16A1/MCT1histone deacetylase (HDAC) inhibitioninflammatory bowel diseases (IBD)monocytes/macrophages

Identifiers

PMID41110099
PMCPMC12631161

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.