Research now suggests that the microbiota — commensal microorganisms including bacteria, fungi, and viruses that inhabit an organism — plays an important role in carcinogenesis, cancer progression, and treatment response.1
Though most evidence for the association between the microbiota and cancer comes from studies using animal models, some studies in humans also support these findings. The effect of modulation of the microbiome to prevent, treat, or enhance outcomes with conventional therapies, and how to do so, is still under investigation.
The microorganism-human cell ratio is about 10:1 and the number of microbial genes present within the human body is 100-fold greater than human genes. It is now known that the microbiota is instrumental in multiple normal human processes, including immune system development, immunity, and detoxification of dietary components, among others.1,2
Dysbiosis — or permanent deviation of the composition and function of the microbiota and the relationship between the microbiota and its host — was also associated with multiple pathologies.1 One such pathology is cancer.
Data From Animal Models
Several lines of evidence among animal models suggest that disturbances in the microbiota affect carcinogenesis and antitumor treatment response.
Mice that do not produce or respond to interleukin (IL)-8, or who have impaired immune function for genetic reasons, have intestinal dysbiosis and demonstrate a greater susceptibility to chemically-induced colon cancer. In one study, colon polyps in mice had increased epithelial barrier permeability and transmucosal bacterial translocation. In this study, translocation of the microbiota resulted in polyp progression.
A dysbiosis in which a particularly microorganism is elevated has been associated with increased carcinogenesis in intestinal and colon, mammary, prostate, and liver cancers.
Several studies demonstrated that response to chemotherapy may be modulated by the gut microbiota.1
Data from one study suggests that gut bacteria prime directly or indirectly tumor-infiltrating myeloid cells. Another study demonstrated that the efficacy of oxaliplatin and cisplatin against a sterile transplanted subcutaneous tumor was impaired by antibiotic treatment. This effect was likely due to suppression of early genotoxic effects of these agents. Antibiotic treatment also impaired oxaliplatin-induced gene expression or downregulation, which is a component of the anticancer activity of the drug.
Another study demonstrated that the efficacy of cyclophosphamide is reduced by antibiotic treatment, and cyclophosphamide treatment changes the composition of the intestinal microbiota.