The role of gut microbial β-glucuronidases in carcinogenesis and cancer treatment: a scoping review

Abstract

Introduction: The human gut microbiota influence critical functions including the metabolism of nutrients, xenobiotics, and drugs. Gut microbial β-glucuronidases (GUS) enzymes facilitate the removal of glucuronic acid from various compounds, potentially affecting anti-cancer drug efficacy and reactivating carcinogens. This review aims to comprehensively analyze and summarize studies on the role of gut microbial GUS in cancer and its interaction with anti-cancer treatments. Its goal is to collate and present insights that are directly relevant to patient care and treatment strategies in oncology. Methods: This scoping review followed PRISMA-ScR guidelines and focused on primary research exploring the role of GUS within the gut microbiota related to cancer etiology and anti-cancer treatment. Comprehensive literature searches were conducted in PubMed, Embase, and Web of Science. Results: GUS activity was only investigated in colorectal cancer (CRC), revealing increased fecal GUS activity, variations in the gut microbial composition, and GUS-contributing bacterial taxa in CRC patients versus controls. Irinotecan affects gastrointestinal (GI) health by increasing GUS expression and shifting gut microbial composition, particularly by enhancing the presence of GUS-producing bacteria, correlating with irinotecan-induced GI toxicities. GUS inhibitors (GUSi) can mitigate irinotecan's adverse effects, protecting the intestinal barrier and reducing diarrhea. Conclusion: To our knowledge, this is the first review to comprehensively analyze and summarize studies on the critical role of gut microbial GUS in cancer and anti-cancer treatment, particularly irinotecan. It underscores the potential of GUSi to reduce side effects and enhance treatment efficacy, highlighting the urgent need for further research to integrate GUS targeting into future anti-cancer treatment strategies.