Microbiome in cancer progression and therapy

Abstract

A myriad of microbes living together with the host constitute microbiota, which possesses very diverse functions in regulation of host physiology. Recently, it has been unequivocally demonstrated that microbiota regulates cancer initiation, progression and responses to therapy. Here we review known pro-tumorigenic and anti-tumorigenic function of microbiota and mechanisms how microbes can regulate cancer cells and immune and stromal cells within the tumor microenvironment.

Figure 1. Roles of «beneficial» and «pathogenic» bacteria in primary tumor development and metastasis

Microbiota contains multiple species with different metabolic activities and other properties, and these species co-exist with the host within the particular niche or tissue. Each relevant bacterial species plays the different role in the primary tumor growth, metastasis and anti-cancer therapy. «Beneficial» bacteria can suppress tumor growth and improve anti-cancer therapies through several direct mechanisms but also can inhibit overgrowth and outcompete «pathogenic» bacteria in the context of cancer. Pathogenic bacteria promote tumor development, metastasis and resistance to therapies. “Green” reflects anti-tumorigenic action, while “Red” is tumor-promoting function. Arrows illustrate active promotion, while blocks illustrate inhibition. Figure was produced using BioRender platform.

Figure 2. Mechanisms of microbiota-host interactions promoting tumorigenesis

Non-modifiable (genetic) and environmental factors promote intestinal epithelial barrier disruption and dysbiosis. Barrier dysfunction causes bacterial penetration through the epithelium and their interaction with host cells by several mechanisms: (1) immune cell activation and triggering of pro-tumorigenic inflammation; (2) Epithelial cell DNA damage by bacterial toxins or bacteria-induced genotoxic products (e.g. ROS) ; (3) modulation of immune, stromal and cancer cell function through the effect of bacterial metabolites acting locally or distantly. Figure was produced using BioRender platform.