ArticleSurgical infections
Microbial Glucuronidase Inhibition Reduces Severity of Diclofenac-Induced Anastomotic Leak in Rats.
Article in Surgical infections. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Sex-dependent responses in mice to indomethacin-induced organ injury and gut microbiome-targeted alleviation.Scientific reports · 2025Article
- Emerging gut microbial glycoside hydrolase inhibitors.RSC chemical biology · 2025Review
- Gut bacteria and the host synergies promote resveratrol metabolism and induce tolerance in ALD mice.NPJ biofilms and microbiomes · 2025Article
- Impact of gut microbiota on colorectal anastomotic healing (Review).Molecular and clinical oncology · 2025Review
- Commercially Purchased and In-House Bred C57BL/6 Mice with Different Gut Microbiota Exhibit Distinct Indomethacin-Induced Toxicities.Gut microbes reports · 2025Article
- Advanced piperazine-containing inhibitors target microbial β-glucuronidases linked to gut toxicity.RSC chemical biology · 2024Article
- Perioperative Considerations for the Surgical Treatment of Crohn's Disease with Discussion on Surgical Antibiotics Practices and Impact on the Gut Microbiome.Antibiotics (Basel, Switzerland) · 2024Review
- Drug-microbiota interactions: an emerging priority for precision medicine.Signal transduction and targeted therapy · 2023Review
- Microbial β-glucuronidases drive human periodontal disease etiology.Science advances · 2023Article
- The Influence of the Microbiome on Anastomotic Leak.Clinics in colon and rectal surgery · 2023Review
- Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice.Scientific reports · 2022Article
- A structural metagenomics pipeline for examining the gut microbiome.Current opinion in structural biology · 2022Review
- Influence of the Microbiome on Anastomotic Leak.Clinics in colon and rectal surgery · 2021Review
- Drug Response Diversity: A Hidden Bacterium?Journal of personalized medicine · 2021Review
- Predicting drug-metagenome interactions: Variation in the microbial β-glucuronidase level in the human gut metagenomes.PloS one · 2021Article
- Targeted inhibition of gut bacterial β-glucuronidase activity enhances anticancer drug efficacy.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Relationship Between the Gut Microbiome and Systemic Chemotherapy.Digestive diseases and sciences · 2020Review
- Therapeutic significance of β-glucuronidase activity and its inhibitors: A review.European journal of medicinal chemistry · 2020Review
- Targeting gut microbiota for precision medicine: Focusing on the efficacy and toxicity of drugs.Theranostics · 2020Review
- Active site flexibility revealed in crystal structures of Parabacteroides merdae β-glucuronidase from the human gut microbiome.Protein science : a publication of the Protein Society · 2018Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe non-steroidal anti-inflammatory drug diclofenac has been associated with intestinal anastomotic leakage, although the underlying pathophysiology is unclear. Previous data suggest that reactivation of biliary diclofenac metabolites by microbial β-glucuronidases in the gut plays a role in harming the intestinal mucosa, and that microbiome-targeted glucuronidase inhibition prevents this damage. Here, the microbial glucuronidase inhibitor Inh1 was examined for its ability to reduce diclofenac-induced anastomotic leakage in rats.
methodsNinety male Wistar rats were allocated to five groups. In the two diclofenac groups, group DCF received diclofenac (3 mg/kg per day) and group DCF-Inh1 additionally received 800 mcg/kg per day of glucuronidase inhibitor Inh1 solution orally. In non-diclofenac groups, animals received either Inh1 (800 mcg/kg per day; group Inh1) solution, the vehicle (methylcellulose; group Veh), or no solution (group Ctrl). All solutions were provided from the day of surgery until sacrifice on day three. Plasma concentrations of diclofenac were determined. Outcomes were anastomotic leakage, leak severity, and anastomotic strength.
resultsAnastomotic leak rates were 89% in group DCF and 44% in group DCF-Inh1 (p = 0.006). Leak severity was reduced in group DCFic-Inh1 (p = 0.029). In non-diclofenac cohorts, mostly minor leakage signs were observed in 25% in group Ctrl, 39% in group Inh1 (0.477), and 24% in group Veh (p = 1.000). Bursting pressure and breaking strength were not significantly different. Plasma concentrations of diclofenac were not changed by Inh1.
conclusionMicrobial glucuronidase inhibitor reduces diclofenac-induced anastomotic leakage severity, which suggests a harmful effect of diclofenac metabolite reactivation in the gut. This finding improves the understanding of the pathogenesis of anastomotic leakage.
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