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

Matthew R Redinbo, Judith de Vos-Geelen, Marjolein L Smidt, John Penders, Lars E Hillege, Milou A M Stevens, Paulien A J Kristen

Journal: Journal of cancer research and clinical oncology 2024;150(11):495

PMID: 39537966

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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.

Address: GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands. [email protected].; Department of Surgery, FHML, Maastricht University Medical Center+, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, the Netherlands. [email protected].; GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.; Department of Surgery, FHML, Maastricht University Medical Center+, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, the Netherlands.; GROW - School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.; Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands.; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.; Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, the Netherlands.; Departments of Chemistry, Biochemistry & Biophysics, and Microbiology & Immunology, University of North Carolina, Chapel Hill, NC, USA.

DOI: 10.1007/s00432-024-06028-2

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https://dx.doi.org/10.1007/s00432-024-06028-2

MeSH Terms: Humans, Gastrointestinal Microbiome, Carcinogenesis, Glucuronidase, Neoplasms, Antineoplastic Agents