Evidence map›Paper›PMID 41110769›Full record

ArticleMolecular metabolism2025

The diet-derived gut microbial metabolite 3-phenylpropionic acid reverses insulin resistance and obesity-associated metabolic dysfunction.

Sara Alqudah, Beckey DeLucia, Lucas J Osborn, Rachel L Markley, Viharika Bobba, Sarah M Preston, Tharika Thambidurai, Layan Hamidi Nia, Clifton G Fulmer, Naseer Sangwan and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Sara AlqudahDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Chemistry, Cleveland State University, Cleveland, OH, USA.
Beckey DeLuciaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA.
Lucas J OsbornDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Rachel L MarkleyDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA.
Viharika BobbaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA.
Sarah M PrestonDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Tharika ThambiduraiDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Biology, Case Western Reserve University, Cleveland, OH, USA.
Layan Hamidi NiaDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Chemical and Biomedical Engineering, Cleveland State University, Cleveland, OH, USA.
Clifton G FulmerDepartment of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute of the Cleveland Clinic, Cleveland, OH, USA.
Naseer SangwanDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA.
Ina NemetDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA.
Jan ClaesenDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH, USA; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. Electronic address: claesej@ccf.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background/purposeObesity-associated metabolic disorders, including type 2 diabetes and metabolic dysfunction associated fatty liver disease (MAFLD), are major global health burdens. While dietary polyphenols have shown promise in ameliorating these conditions, their efficacy is dependent on specialized gut microbial metabolism, and the underlying molecular mechanisms remain mostly elusive. Here, we demonstrate that dietary supplementation with polyphenol-rich elderberry (Eld) extract abrogates the effects of an obesogenic diet in a gut microbiota-dependent manner, preventing insulin resistance and reducing hepatic steatosis in mice.

methodsWe developed a targeted, quantitative liquid chromatography-tandem mass spectrometry method for detection of gut bacterial polyphenol catabolites and identified 3-phenylpropionic acid as a key microbial metabolite in the portal plasma of Eld supplemented animals.

resultsWe showed that 3-phenylpropionic acid potently activates hepatic AMP-activated protein kinase α, explaining its role in improved liver lipid homeostasis. We further uncovered the metabolic pathway cumulating in 3-phenylpropionic acid for the common gut commensal Clostridium sporogenes.

conclusionOur findings establish 3-phenylpropionic acid as a diet-derived, microbiota-dependent metabolite with insulin-sensitizing and anti-steatotic activities and provide a molecular basis for prebiotic interventions to improve host metabolic health.

Indexed as

Gastrointestinal MicrobiomeInsulin ResistanceObesityPhenylpropionatesAnimalsDiet, High-FatFatty LiverLiverMaleMiceMice, Inbred C57BLPolyphenolsPropionates3-phenylpropionic acidPhenylpropionatesPolyphenolsPropionates3-Phenylpropionic acidGut microbiomeHepatic steatosisInsulin resistanceMAFLDObesityType 2 diabetes

Identifiers

PMID41110769
PMCPMC12615361

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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.