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Adv. Drug Deliv. Rev., May 15 2024, 210 S0169-409X(24)00154-6 | https://doi.org/10.1016/j.addr.2024.115332 Novel strategies for modulating the gut microbiome for cancer therapy

Young Seok Cho ^a,b,1, Kai Han ^e,f,1, Jin Xu ^a,b,1, James J. Moon ^a,b,c,d

^aDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109, USA

^bBiointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA

^cDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA

^dDepartment of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA

^eState Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 21009, China

^fJiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China

¹Authors contributed equally.

Corresponding author : James J. Moon

Abstract

Recent advancements in genomics, transcriptomics, and metabolomics have significantly advanced our understanding of the human gut microbiome and its impact on the efficacy and toxicity of anti-cancer therapeutics, including chemotherapy, immunotherapy, and radiotherapy. In particular, prebiotics, probiotics, and postbiotics are recognized for their unique properties in modulating the gut microbiota, maintaining the intestinal barrier, and regulating immune cells, thus emerging as new cancer treatment modalities. However, clinical translation of microbiome-based therapy is still in its early stages, facing challenges to overcome physicochemical and biological barriers of the gastrointestinal tract, enhance target-specific delivery, and improve drug bioavailability. This review aims to highlight the impact of prebiotics, probiotics, and postbiotics on the gut microbiome and their efficacy as cancer treatment modalities. Additionally, we summarize recent innovative engineering strategies designed to overcome challenges associated with oral administration of anti-cancer treatments. Moreover, we will explore the potential benefits of engineered gut microbiome-modulating approaches in ameliorating the side effects of immunotherapy and chemotherapy.

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