Evidence map›Paper›PMID 39778875›Full record

ArticleACS chemical biology2025

A Small-Molecule Inhibitor of Gut Bacterial Urease Protects the Host from Liver Injury.

Khyle C Richards-Corke, Yindi Jiang, Vladimir Yeliseyev, Yancong Zhang, Eric A Franzosa, Zhipeng A Wang, Maheeshi Yapa Abeywardana, Phillip A Cole, Curtis Huttenhower, Lynn Bry and 1 more

Abstract readLetter
In one paragraph

Article in ACS chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. [Research advances on hepatic encephalopathy following transjugular intrahepatic portosystemic shunt].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
    Review
  3. Review
  4. Article
  5. Article
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

11 authors.

Khyle C Richards-CorkeHarvard University, Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, United States.ORCID 0000-0002-5433-0115
Yindi JiangHarvard University, Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, United States.
Vladimir YeliseyevBrigham and Women's Hospital, Massachusetts Host-Microbiome Center, Department of Pathology, Boston, Massachusetts 02115, United States.
Yancong ZhangInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.ORCID 0000-0002-2768-2975
Eric A FranzosaInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
Zhipeng A WangDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States.ORCID 0000-0002-5693-7359
Maheeshi Yapa AbeywardanaDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States.
Phillip A ColeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, United States.ORCID 0000-0001-6873-7824
Curtis HuttenhowerInfectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, United States.
Lynn BryBrigham and Women's Hospital, Massachusetts Host-Microbiome Center, Department of Pathology, Boston, Massachusetts 02115, United States.
Emily P BalskusHarvard University, Department of Chemistry and Chemical Biology, Cambridge, Massachusetts 02138, United States.ORCID 0000-0001-5985-5714

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
A comprehensive platform for novel therapy development from the microbiomeR24DK110499 · NIDDK · BROAD INSTITUTE, INC. · PI HUTTENHOWER, CURTIS · 2017 to 2021
$7.7M
Commensal control of C. difficile virulenceR01AI153605 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI BRY, LYNN · 2021 to 2025
$3.4M
Chemical Approaches to Understanding Reversible Lysine ModificationsR35GM149229 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI PHILIP A COLE · 2023 to 2026
$1.9M
Howard Hughes Medical Institute 20380529NIAID NIH HHS R01 AI153605NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R24 DK110499NIGMS NIH HHS R35 GM149229
6 · The paper itself

Abstract

Hyperammonemia is characterized by the accumulation of ammonia within the bloodstream upon liver injury. Left untreated, hyperammonemia contributes to conditions such as hepatic encephalopathy that have high rates of patient morbidity and mortality. Previous studies have identified gut bacterial urease, an enzyme that converts urea into ammonia, as a major contributor to systemic ammonia levels. Here, we demonstrate use of benurestat, a clinical candidate used against ureolytic organisms in encrusted uropathy, to inhibit urease activity in gut bacteria. Benurestat inhibits ammonia production by urease-encoding gut bacteria and is effective against individual microbes and complex gut microbiota. When administered to conventional mice with liver injury induced by thioacetamide exposure, benurestat reduced gut and serum ammonia levels and rescued 100% of mice from lethal acute liver injury. Overall, this study provides an important proof-of-concept for modulating host ammonia levels and microbiota-driven risks for hyperammonemia with gut microbiota-targeted small-molecule inhibitors.

Indexed as

Gastrointestinal MicrobiomeUreaseAmmoniaAnimalsBacteriaChemical and Drug Induced Liver InjuryEnzyme InhibitorsHyperammonemiaLiverMaleMiceMice, Inbred C57BLSmall Molecule LibrariesAmmoniaEnzyme InhibitorsSmall Molecule LibrariesUrease

Identifiers

PMID39778875
PMCPMC11744669

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.