ArticleBritish journal of pharmacology2023
Opioid-induced microbial dysbiosis disrupts irinotecan (CPT-11) metabolism and increases gastrointestinal toxicity in a murine model.
Article in British journal of pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 19 citations in OpenAlex.
- Drug-microbiome-host interactions: antimicrobial effects of non-antibiotic compounds.Nature reviews. Gastroenterology & hepatology · 2026Review
- Gut Microbiota Metabolic Reprogramming Drives Endocrine and Immune Resistance in Hormone-Dependent Cancers.Cancers · 2026Review
- The Early Safety Signal of Sacituzumab Govitecan-Related Toxicity and theJournal of clinical medicine · 2026Article
- 6-Shogaol from Banxia Xiexin Tang: A Potent Regulator of Th17/Treg Balance to Protect Against CPT-11-Induced Intestinal Mucosal Damage.Journal of microbiology and biotechnology · 2026Article
- From bugs to behavior: targeting the gut-brain interface for addiction therapeutics.Gut microbes · 2025Review
- Microbiome dysbiosis and chemotherapy resistance in acute myeloid leukemia (AML).NPJ biofilms and microbiomes · 2025Review
- Butyrate prevents chemotherapy-induced gastrointestinal toxicity and microbial dysbiosis.Scientific reports · 2025Article
- Butyrate Modulates Intestinal Microbiome and Epithelial Function to Attenuate Irinotecan-induced GI Toxicity.Research square · 2025Article
- The role of the gut microbiota in chemotherapy response, efficacy and toxicity: a systematic review.NPJ precision oncology · 2025Article
- β-Glucuronidase-Expressing Lactobacillus reuteri Triggers Irinotecan Enterotoxicity Through Depleting the Regenerative Epithelial Stem/Progenitor Pool.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Pharma[e]cology: How the Gut Microbiome Contributes to Variations in Drug Response.Annual review of pharmacology and toxicology · 2025Review
- Intestinal immunoglobulins under microbial dysbiosis: implications in opioid-induced microbial dysbiosis.Frontiers in microbiology · 2025Review
- The interplay between the microbiota and opioid in the treatment of neuropathic pain.Frontiers in microbiology · 2024Review
- Changes in Plasma Metabolic Signature upon Acute and Chronic Morphine Administration in Morphine-Tolerant Mice.Metabolites · 2023Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
background and purposeOpioids are commonly used for the management of cancer-associated pain and chemotherapy-induced diarrhoea. The chemotherapeutic irinotecan (CPT-11) causes severe gastrointestinal (GI) toxicity due to deconjugation of inactive metabolite SN-38 glucuronide (SN-38G) by bacterial β-glucuronidases to the active 7-ethyl-10-hydroxycamptothecin (SN-38). Opioids are known to cause gut microbial dysbiosis, this study evaluated whether CPT-11 anti-tumour efficacy and GI toxicity are exacerbated by opioid co-administration. EXPERIMENTAL APPROACH: Eight-week-old C57BL/6 male mice were co-administration with CPT-11 ± opioid. 16S rRNA sequencing was used for gut microbiome analysis. LC-MS analyses of plasma and intestinal extracts were performed to investigate the pharmacokinetic profile of CPT-11. Histological analysis and quantitative real-time polymerase chain reaction were used to determine the severity of intestinal tissue damage. Human liver microsome In vitro assay was performed to confirm the effects of opioids on CPT-11 metabolism. KEY
resultsGut microbiome analysis showed that morphine treatment induced enrichment of β-glucuronidase-producing bacteria in the intestines of CPT-11-treated mice, resulting in SN-38 accumulation and exacerbation of GI toxicity in the small intestine. Oral administration of both antibiotics and glucuronidase inhibitor protected mice against GI toxicity induced with CPT-11 and morphine co-administration, implicating a microbiome-dependent mechanism. Additionally, morphine and loperamide decreased the plasma concentration of SN-38 and compromised CPT-11 anti-tumour efficacy, this seemed to be microbiome independent. CONCLUSION AND IMPLICATIONS: Gut microbiota play a significant role in opioid and chemotherapeutic agent drug-drug interactions. Inhibition of gut microbial glucuronidase may also prevent adverse GI effects of CPT-11 in patients on opioids.
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.