Introduction: Human microbiota is dynamic mixture of microorganisms, including bacteria, fungi, and viruses, that is important for the maintenance of homeostasis. The gut microbiome refers to microbiota located in the gastrointestinal tract with various biochemical activities. When the balance between the gut microbiome and the host is disturbed, metabolic products and secretory vesicles change, which results to the occurrence and maintenance of physiological disorders such as cancer. In the present work, we focused on the role of gut microbiome in the induction and therapy resistance of human cancers. Search Method: Recent review articles including keywords gut microbiota, cancer occurrence and chemotherapy resistance were extracted from databases Google Scholar, Web of Science and PubMed. Results: Gut microbiota are involved in cancer occurrence, since they produce metabolites that induce DNA damage and epigenetics alterations, trigger aberrant signaling pathways and/or elicit immunosuppressive effects. Studying colon, prostate, breast and stomach carcinomas revealed that Bacteroides, Fusobacterium, Bacillus, Staphylococcus, Proteobacteria and Lactobacillus acted as cancer-causing microbiota. On the other hand, gut microbiota affect chemotherapy outcome via numerous mechanisms such as the xeno metabolism of anti-cancer drugs. In this regard, it has been reported that Bacteroides species increased side effects and toxicity of 5- fluorouracil (5- FU)-sorivudine bi-therapy, as they converted sorivudine, inhibited the degradation of 5-FU and thus, accumulated drugs in the blood circulation. In addition, intratumoral bacteria could reduce the efficacy of chemotherapy via their active metabolic functions. For instance, the thymidine phosphorylase activity of Mycoplasma led to reduced cytotoxicy of pyrimidine nucleoside analogs. Likewise, cytidine deaminase from Gammaproteobacteria induced gemcitabine resistance in cancer cells. Conclusion: Gut microbiota could be considered as significant personalized biomarkers that help clinicians to identify dysbiotic states associated with poor therapeutic outcomes and/or identify suitable microbial targets for modification.

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