Evidence mapPaperPMID 39580049Full record

ReviewMetabolism: clinical and experimental2025

Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome.

Zachary A Kipp, Olufunto O Badmus, David E Stec, Brantley Hall, Terry D Hinds

Abstract readReview
In one paragraph

Review in Metabolism: clinical and experimental, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Metabolites · 2026
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  19. Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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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

5 authors.

Zachary A KippDrug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
Olufunto O BadmusDepartment of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA.
David E StecDepartment of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA.
Brantley HallCenter for Bioinformatics and Computational Biology, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA.
Terry D HindsDrug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA. Electronic address: Terry.Hinds@uky.edu.

Funding

Sex differences in operant cocaine memoriesP20GM144041 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · 2023 to 2025
$6.7M
Pilot Projects ProgramP30GM149404 · UNIVERSITY OF MISSISSIPPI MED CTR · 2025 to 2025
$1.2M
Integrative Role of Bilirubin on ObesityR01DK121748 · NIDDK · UNIVERSITY OF MISSISSIPPI MED CTR · PI DAVID E STEC · 2022 to 2023
$994k
Neurobehavioral mechanisms underlying xylazine and fentanyl co-use and withdrawalR01DA058933 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$497k
Bilirubin Catabolism induces Plasminogen-Activator Inhibitor 1 (PAI-1) worsening Metabolic DysfunctionF31HL170972 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$36k
NHLBI NIH HHS F31 HL170972NIDA NIH HHS R01 DA058933NIDDK NIH HHS R01 DK121748NIDDK NIH HHS R01 DK121797NIGMS NIH HHS P20 GM104357NIGMS NIH HHS P20 GM144041NIGMS NIH HHS P30 GM149404
6 · The paper itself

Abstract

The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.

Indexed as

BilirubinBiomarkersInsulin ResistanceKidneyLiverAnimalsCardiovascular DiseasesGastrointestinal MicrobiomeHumansMetabolic SyndromeBilirubinBiomarkersAntioxidantBilirubin reductaseBiliverdin reductaseBilRBLVRAHeme oxygenaseHMOX1MASLDMicrobiomeObesity

Identifiers

PMID39580049
PMCPMC11700773

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.