ArticleACS central science2018
Gut Microbial β-Glucuronidase Inhibition via Catalytic Cycle Interception.
Article in ACS central science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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.
Who cites it
41 citing papers in PubMed, 73 citations in OpenAlex.
- High-throughput identification of bacterial β-glucuronidase inhibitors using machine learning.Gut microbes · 2026Article
- Phenotypic high-throughput screening identifies modulators of gut microbial choline metabolism.mBio · 2026Article
- Gut Microbiota Mediate the Metabolism of Colonic Prostaglandins.Research square · 2026Article
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- Phase IV Metabolism: Gut Microbial Metabolism of Common Gastrointestinal Drugs.Gastroenterology clinics of North America · 2025Review
- Natural Flavonoids from Licorice as Potent Inhibitors of β-Glucuronidase Elucidated Through Computational Studies.Molecules (Basel, Switzerland) · 2025Article
- Probing and manipulating the gut microbiome with chemistry and chemical tools.Gut microbiome (Cambridge, England) · 2025Review
- Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity.RSC chemical biology · 2024Article
- Gut microbial β-glucuronidases influence endobiotic homeostasis and are modulated by diverse therapeutics.Cell host & microbe · 2024Article
- Synthesis, characterization, Hirshfeld surface analysis, antioxidant and selective β-glucuronidase inhibitory studies of transition metal complexes of hydrazide based Schiff base ligand.Scientific reports · 2024Article
- A New Paradigm in the Relationship between Gut Microbiota and Breast Cancer: β-glucuronidase Enzyme Identified as Potential Therapeutic Target.Pathogens (Basel, Switzerland) · 2023Review
- Microbial β-glucuronidases drive human periodontal disease etiology.Science advances · 2023Article
- Targeting the human gut microbiome with small-molecule inhibitors.Nature reviews. Chemistry · 2023Review
- Irinotecan-gut microbiota interactions and the capability of probiotics to mitigate Irinotecan-associated toxicity.BMC microbiology · 2023Article
- Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice.Scientific reports · 2022Article
- Pharmacological hypothesis: A recombinant probiotic for taming bacterial β-glucuronidase in drug-induced enteropathy.Pharmacology research & perspectives · 2022Article
- The role of gut microbial β-glucuronidase in drug disposition and development.Drug discovery today · 2022Review
- Carbohydrate-active enzymes (CAZymes) in the gut microbiome.Nature reviews. Microbiology · 2022Review
- TheXenobiotica; the fate of foreign compounds in biological systems · 2022Article
- A structural metagenomics pipeline for examining the gut microbiome.Current opinion in structural biology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Microbial β-glucuronidases (GUSs) cause severe gut toxicities that limit the efficacy of cancer drugs and other therapeutics. Selective inhibitors of bacterial GUS have been shown to alleviate these side effects. Using structural and chemical biology, mass spectrometry, and cell-based assays, we establish that piperazine-containing GUS inhibitors intercept the glycosyl-enzyme catalytic intermediate of these retaining glycosyl hydrolases. We demonstrate that piperazine-based compounds are substrate-dependent GUS inhibitors that bind to the GUS-GlcA catalytic intermediate as a piperazine-linked glucuronide (GlcA, glucuronic acid). We confirm the GUS-dependent formation of inhibitor-glucuronide conjugates by LC-MS and show that methylated piperazine analogs display significantly reduced potencies. We further demonstrate that a range of approved piperazine- and piperidine-containing drugs from many classes, including those for the treatment of depression, infection, and cancer, function by the same mechanism, and we confirm through gene editing that these compounds selectively inhibit GUS in living bacterial cells. Together, these data reveal a unique mechanism of GUS inhibition and show that a range of therapeutics may impact GUS activities in the human gut.
Identifiers
What OpenQuestion holds
Registered trials
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.