Evidence map›Paper›PMID 41447757›Full record

ArticleEBioMedicine2026

Reprogramming offspring liver health: maternal indole supplementation as a preventive strategy against MASLD.

Ashok Mandala, Ram Babu Undi, Rachel C Janssen, Kameron Y Sugino, Wanke Zhao, Benjamin N Nelson, April M Teague, Nikhil Y Patil, Karin Zemsky Berry, Rohan Varshney and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

16 authors.

Ashok MandalaHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Ram Babu UndiHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Rachel C JanssenHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Kameron Y SuginoHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Wanke ZhaoHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Benjamin N NelsonHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
April M TeagueHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Nikhil Y PatilHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Pharmaceutical Sciences, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Karin Zemsky BerryDivision of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Rohan VarshneyHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Bryan C BergmanDivision of Endocrinology, Diabetes, and Metabolism, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Michael C RudolphHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Campus, 975 NE 10th St, Oklahoma City, OK, USA.
Aditya D JoshiHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Pharmaceutical Sciences, University of Oklahoma Health Campus, Oklahoma City, OK, USA.
Raju V S RajalaHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Campus, 975 NE 10th St, Oklahoma City, OK, USA.
Karen R JonscherHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Campus, 975 NE 10th St, Oklahoma City, OK, USA; Department of Obstetrics and Gynecology, University of Oklahoma Health Campus, Oklahoma City, OK, USA. Electronic address: karen-jonscher@ou.edu.
Jacob E FriedmanHarold Hamm Diabetes Center, University of Oklahoma Health Campus, Oklahoma City, OK, USA; Department of Biochemistry and Physiology, University of Oklahoma Health Campus, 975 NE 10th St, Oklahoma City, OK, USA; Division of Endocrinology, Diabetes and Metabolism, Department of Pediatrics, University of Oklahoma Health Campus, Oklahoma City, OK, USA. Electronic address: jed-friedman@ou.edu.

Funding

PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI BRYAN C BERGMAN · 1995 to 2026
$32.6M
Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI James F Papin · 2018 to 2026
$27.1M
Mentoring Translational Cancer Research in OklahomaP30GM154635 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Rajagopal Ramesh · 2024 to 2026
$4.3M
Novel Mechanism of aryl hydrocarbon receptor-mediated differential gene regulationR01DK122028 · NIDDK · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Aditya D Joshi · 2019 to 2026
$2.3M
Role of the Macrophage in Developmentally Programmed NAFLDR01DK121951 · NIDDK · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FRIEDMAN, JACOB E, JONSCHER, KAREN R · 2020 to 2023
$2.3M
NCI NIH HHS P30 CA225520NIDDK NIH HHS P30 DK048520NIDDK NIH HHS R01 DK121951NIDDK NIH HHS R01 DK122028NIGMS NIH HHS P30 GM154635
6 · The paper itself

Abstract

backgroundDisruptions in early-life gut microbiota and metabolites associated with maternal Western-style diet (WD) during critical windows of development are linked to metabolic and inflammatory diseases in offspring, including metabolic dysfunction-associated steatotic liver disease (MASLD) in later life. These disturbances can alter microbial metabolite production, such as tryptophan derivatives, which are crucial for immune and metabolic regulation. However, the specific effects of maternal supplementation with tryptophan metabolites on offspring gut microbiome maturation and MASLD risk remain unexplored.

methodsWD-fed mouse dams were supplemented with microbial metabolites indole (Ind) or indole-3-acetic acid (I3A) during gestation and lactation; male offspring were weaned to chow diet for 9 weeks, followed by a 4-week WD challenge. Fecal microbiota transfer (FMT) was performed from offspring to naïve recipients, followed by a 4-week WD challenge. Human LX-2 stellate cells were used to study mechanisms for indole and very long-chain (VLC) ceramide effects on TGF-β-induced fibrosis.

findingsMaternal supplementation with Ind or I3A had long-term protective effects in adult WD-challenged offspring against excess weight gain, steatosis, stellate cell activation, and fibrosis. Perinatal exposure to Ind or I3A activated offspring aryl hydrocarbon receptor (AHR) signalling in gut and liver, which trans-repressed known and new target genes, including ceramidases Asah2 and Acer3, leading to increased VLC ceramides. FMT from offspring with perinatal exposure to Ind protected recipients from WD-induced fibrogenesis and increased beneficial VLC ceramides in recipient livers. In vitro, LX-2 stellate cells cultured with Ind or VLC ceramides demonstrated an anti-fibrotic effect, which was abolished by AHR inhibition.

interpretationMaternal indole supplementation, through sustained activation of AHR in offspring gut and liver and an increase in hepatic VLC ceramides, prevents diet-induced MASLD and fibrosis in offspring, offering a novel therapeutic pathway for prevention of paediatric MASLD.

fundingSee Acknowledgements.

Indexed as

Dietary SupplementsFatty LiverIndolesLiverAnimalsCeramidesDiet, WesternDisease Models, AnimalFecal Microbiota TransplantationFemaleGastrointestinal MicrobiomeHepatic Stellate CellsHumansIndoleacetic AcidsMaleMaternal ExposureCeramidesindoleindoleacetic acidIndoleacetic AcidsIndolesReceptors, Aryl HydrocarbonAryl hydrocarbon receptor (AHR)CeramidesDevelopmental programmingFecal microbiota transferMetabolic dysfunction-associated steatotic liver diseaseMicrobiomeTryptophan

Identifiers

PMID41447757
PMCPMC12799784

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.