ArticleProceedings of the National Academy of Sciences of the United States of America2020
Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 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
118 citing papers in PubMed, 189 citations in OpenAlex.
- The cervicovaginal gut microbiota axis as a key determinant of systemic physiology.Gut microbes · 2026Review
- Tamoxifen induced hepatotoxicity via gut microbiota-mediated hyodeoxycholic acid depletion and Farnesoid X receptor signaling disruption.Gut microbes · 2026Article
- Decoding the cancer microbiome: multi-omics, AI, and translational opportunities.Genome biology · 2026Review
- Ingestible probes for breath-based monitoring of drug-metabolizing activity from the microbiome.Science advances · 2026Article
- Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.Journal of neuroinflammation · 2026Article
- The Gut Microbiome Dependency Continuum in Drug Discovery: A Unified Pharmacology Framework Linking Clinical Drugs, Natural Products, and Engineered Microbial Therapeutics.Biotech (Basel (Switzerland)) · 2026Review
- Glucuronidation metabolomic fingerprinting to map host-microbe metabolism.Nature communications · 2026Article
- A drug-microbiome-drug interaction impacts co-prescribed medications for Parkinson's disease.Nature microbiology · 2026Article
- Data-driven prioritization of mouse strains for improved preclinical modeling of rare and common disease.bioRxiv : the preprint server for biology · 2026Article
- Microbiome-Modulating Strategies in Anticancer Therapy: A Review of Current Evidence and Recommendations for Further Treatment Improvement.Probiotics and antimicrobial proteins · 2026Review
- The microbial metabolome: remodeling the therapeutic landscape in hematologic malignancies.NPJ biofilms and microbiomes · 2026Review
- β-Glucuronidase at the Microbiota-Host Interface: Dual Regulatory Roles and Precision Modulation by Natural Products.Molecules (Basel, Switzerland) · 2026Review
- Gut microbiota-mediated chemotherapy resistance in colorectal cancer: mechanisms and precision interventions.Frontiers in oncology · 2026Review
- Beyond antibiotics: collateral damage to the gut microbiome during cancer therapy.Frontiers in microbiology · 2026Review
- Metabolism-Driven Modulation by the Human Microbiota: Implications for Cancer Therapy and Emerging Strategies.Advances in experimental medicine and biology · 2026Review
- Development of an adult whole-body PBPK model of irinotecan and its metabolites for predicting UGT1A1/CYP3A-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- Butyrate prevents chemotherapy-induced gastrointestinal toxicity and microbial dysbiosis.Scientific reports · 2025Article
- Characterization of fecal deglucuronidation activity in healthy subjects and in patients treated with fecal microbiota transplantation.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Role of the gut microbiota in the pharmacological effects of traditional Kampo medicine and natural products.Journal of natural medicines · 2025Review
- Gut bacteria-derived metabolites and their implications in mental health and neurological diseases.World journal of microbiology & biotechnology · 2025Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Irinotecan treats a range of solid tumors, but its effectiveness is severely limited by gastrointestinal (GI) tract toxicity caused by gut bacterial β-glucuronidase (GUS) enzymes. Targeted bacterial GUS inhibitors have been shown to partially alleviate irinotecan-induced GI tract damage and resultant diarrhea in mice. Here, we unravel the mechanistic basis for GI protection by gut microbial GUS inhibitors using in vivo models. We use in vitro, in fimo, and in vivo models to determine whether GUS inhibition alters the anticancer efficacy of irinotecan. We demonstrate that a single dose of irinotecan increases GI bacterial GUS activity in 1 d and reduces intestinal epithelial cell proliferation in 5 d, both blocked by a single dose of a GUS inhibitor. In a tumor xenograft model, GUS inhibition prevents intestinal toxicity and maintains the antitumor efficacy of irinotecan. Remarkably, GUS inhibitor also effectively blocks the striking irinotecan-induced bloom of Enterobacteriaceae in immune-deficient mice. In a genetically engineered mouse model of cancer, GUS inhibition alleviates gut damage, improves survival, and does not alter gut microbial composition; however, by allowing dose intensification, it dramatically improves irinotecan's effectiveness, reducing tumors to a fraction of that achieved by irinotecan alone, while simultaneously promoting epithelial regeneration. These results indicate that targeted gut microbial enzyme inhibitors can improve cancer chemotherapeutic outcomes by protecting the gut epithelium from microbial dysbiosis and proliferative crypt damage.
Indexed as
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.