The role of the microbiome in cancer development and therapy

Abstract

The human body harbors an enormous number of microbiota that influence cancer susceptibility, in part, via their prodigious metabolic capacity and their profound influence on immune cell function. Microbial pathogens drive tumorigenesis in 15–20% of cancer cases. An even larger number of malignancies are associated with an altered composition of commensal microbiota (dysbiosis) based on microbiome studies utilizing metagenomic sequencing. Although association studies cannot distinguish whether changes in microbiota are causes or effects of cancer, a causative role is supported by rigorously controlled pre-clinical studies utilizing gnotobiotic mouse models colonized with one or more specific bacteria. These studies demonstrate that microbiota can alter cancer susceptibility and progression by diverse mechanisms such as modulating inflammation, inducing DNA damage, and producing metabolites involved in oncogenesis or tumor suppression. Evidence is emerging that microbiota can be manipulated for improving cancer treatment. By incorporating probiotics as adjuvants for checkpoint immunotherapy or by designing small molecules that target microbial enzymes, microbiota can be harnessed to improve cancer care.

Improve gut microbiome: a new horizon of cancer therapy

“…Gut microbiome has substantial impacts on cancer chemotherapy, immunotherapy and radiotherapy. Even the efficacy of cutting-edge checkpoint inhibitors appears to depend on the patient's gut microbiome (5). The direction indicated by this manuscript and other recent studies on gut microbiome may open a new horizon in cancer therapy.…”

“…However, the suppressions of angiogenesis and tumor growth need another explanation unrelated to IL-17 in this group. Anyway, we should bear in mind that chemotherapy itself alters the composition of microbial communities in patients (5). Moreover, another platinum chemotherapeutic oxaliplatin is known to exerts its tumorretardation effects in a microbiota-dependent manner (5).…”

“…If its effect is further proved for other cancer cells in this model, it may be applied in the prevention and treatment of other cancers in extraintestinal sites. Although the role of probiotics in the cancer therapy still remains adjunctive at present, evidence is emerging that microbiota can be manipulated for improving cancer treatment (5). Gut microbiome has substantial impacts on cancer chemotherapy, immunotherapy and radiotherapy.…”

“…The secondary BA deoxycholic acid (DCA) promotes a condition similar to nonalcoholic steatohepatitis and obesity-associated HCC in a mouse model (5). It perturbs cell membranes to release arachidonic acid, which is converted to reactive oxygen species, potent triggers of inflammation and DNA damage (6).…”

Is Rerum^® the New Coley's Vaccine?

“…Therefore, immunotherapy "should be understood as the activation of a whole system and not a pathway" (Bernichon et al, 2017) where in the concept of a "whole system" microbes of the human microbiota play an essential part. Thus, a very recent paper by researchers of the University of North Carolina describes how "a causative role -for microbes to cause cancer -is supported by rigorously controlled preclinical studies using gnotobiotic mouse models colonized with one or more specific bacteria" and, therefore, "Evidence is emerging that microbiota can be manipulated for improving cancer treatment" (Bhatt et al, 2017). Such a revaluation of the role of microbes in fighting cancer, albeit under a perspective completely different from that of Coley's, may strike a chord in those interested in the recursions of history.…”