Effects of microbiota on anticancer drugs: Current knowledge and potential applications

Abstract

Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).

Keywords: Anticancer drug; Fecal microbiota transplantation; Immune checkpoint inhibitor; Microbiota; Probiotics.

Figure 1

Effects of microbiota on the efficacy and toxicity of anticancer drugs. Bacterial names are color-coded by their association with drug outcomes (green: increased drug efficacy; red: decreased drug efficacy or increased toxicity). A. muciniphila, Akkermansia muciniphila; B. adolescentis, Bifidobacterium adolescent; B. fragilis, Bacteroides fragilis; B. longum, Bifidobacterium longum; B. thetaiotaomicron, Bacteroides thetaiotaomicron; E. faecium, Enterococcus faecium; E. hirae, Enterococcus hirae; B. obeum, Blautia obeum; F. nucleatum, Fusobacterium nucleatum; EGFR, epidermal growth factor receptor.

Figure 2

Flow chart of the literature review process.