Evidence map›Paper›PMID 42612975›Full record

ArticleMolecular metabolism2026

Targeting microbial bile salt hydrolase reprograms bile acid metabolism and ameliorates metabolic dysfunction-associated steatohepatitis in mice.

Wenchao Wei, Radka Graf, Yanhan Wang, Christopher J Oalmann, Jennifer T Lau, Xinyi Wang, Melanie Chien, Mary C Conrad, Jonah Simon, Souradipta Ganguly and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 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

5 · Who and what money

Authors and funding

18 authors.

Wenchao WeiDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Radka GrafVertero Therapeutics, Woburn, MA, USA.
Yanhan WangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Christopher J OalmannVertero Therapeutics, Woburn, MA, USA.
Jennifer T LauVertero Therapeutics, Woburn, MA, USA.
Xinyi WangDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Melanie ChienVertero Therapeutics, Woburn, MA, USA.
Mary C ConradVertero Therapeutics, Woburn, MA, USA.
Jonah SimonVertero Therapeutics, Woburn, MA, USA.
Souradipta GangulyDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Center for Metabolic and Liver Diseases & Cancer Genome and Epigenetics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Tomoo YamazakiDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Aenne HarbertsDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Sainan ChenDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Marcos F FondevilaDepartment of Medicine, University of California San Diego, La Jolla, CA, USA.
Debanjan DharDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Center for Metabolic and Liver Diseases & Cancer Genome and Epigenetics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
A Stewart CampbellVertero Therapeutics, Woburn, MA, USA.
Rebecca K SenterVertero Therapeutics, Woburn, MA, USA. Electronic address: becca@vertero.com.
Bernd SchnablDepartment of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA, USA. Electronic address: beschnabl@ucsd.edu.

Funding

San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LARS ECKMANN, Bernd G. Schnabl · 2019 to 2026
$10.8M
NIDDK NIH HHS P30 DK120515
6 · The paper itself

Abstract

Microbial bile salt hydrolase (BSH) plays a central role in shaping bile acid composition and gut-liver metabolic signaling, yet its therapeutic potential in metabolic dysfunction-associated steatohepatitis (MASH) remains incompletely defined. Here, we evaluated the efficacy of the non-absorbable BSH inhibitor GR-7 in a diet-induced mouse model of steatohepatitis using early and late intervention strategies with different dosing regimens. GR-7 reduced food intake and exerted stage- and dose-dependent therapeutic effects, with early intervention robustly suppressing hepatic fibrosis even at a low dose, whereas late-stage administration of high-dose GR-7 markedly reduced hepatic steatosis and inflammation, as evidenced by decreased liver weight, hepatic triglyceride and cholesterol levels, and plasma ALT. Although late intervention did not result in statistically significant histological reversal of fibrosis, a trend toward improvement was observed, together with suppression of fibrogenic gene expression, suggesting that prolonged treatment may further enhance antifibrotic efficacy. Mechanistically, GR-7 effectively inhibited microbial BSH activity in vivo, leading to reduced cecal unconjugated primary and secondary bile acids-including deoxycholic acid and lithocholic acid, which was associated with improved gut barrier integrity and reduced hepatic inflammation. In parallel, BSH inhibition reprogrammed hepatic bile acid metabolism toward activation of the alternative CYP27A1-mediated synthesis pathway, accompanied by reduced food intake, thereby contributing to reduced hepatic lipid accumulation. Furthermore, late-stage high-dose treatment selectively remodeled the hepatic immune landscape rather than fully restoring homeostasis, highlighting immune recalibration as a key component of therapeutic response. Together, these findings identify microbial BSH inhibition as a promising microbiome-targeted therapeutic strategy for MASH.

Indexed as

AmidohydrolasesBile Acids and SaltsFatty LiverNon-alcoholic Fatty Liver DiseaseAnimalsDisease Models, AnimalGastrointestinal MicrobiomeLiverMaleMiceMice, Inbred C57BLAmidohydrolasesBile Acids and Saltscholoylglycine hydrolaseGut-liver-axisGut microbiomeMASHMicrobiota

Identifiers

PMID42612975
PMCPMC13571960

What OpenQuestion holds

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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.