Microbiome, inflammation, and cancer

Abstract

Inflammation has long been suspected to play a major role in the pathogenesis of cancer. Only recently, however, have some mechanisms of its tumor promoting effects become known. Microbes, both commensal and pathogenic, are critical regulators of the host immune system and, ultimately, of inflammation. Consequently, microbes have the potential power to influence tumor progression as well, through a wide variety of routes, including chronic activation of inflammation, alteration of tumor microenvironment, induction of genotoxic responses, and metabolism. In this review, we will provide a general overview of commensal microbiota, inflammation, and cancer, as well as how microbes fit into this emerging field.

Figure 1. Microbiota distribution in the body and its influence on disease

Normal bacterial composition in various organs of the body (left). Bacterial population increased in dysbiosis are in bold. Cytokines and chemokines upregulated in the process of inflammation and cancer are shown in the right of the figure..

Figure 2. Microbes and Cancer: Therapeutic Avenues

Three potential intervention points to improve patient responses against cancer, along with what the desired effect, and important examples from the literature. (Author: Need reference(s)?)

Figure 3. Summary of Microbial Influence on the Host

A.) Homeostasis. Beneficial bacteria occupy a dominant niche, inhibiting the growth of potentially pathogenic organisms. The integrity of the host organ is maintained and the immune system tolerates and limits bacterial expansion. B.) Barrier Disruption and Inflammation. The barrier integrity of the host organ is compromised, due to tumor growth for example, allowing translocation of bacteria through the barrier, deeper into the organ. This elicits a robust immune response, as immune cells rush into the area, secreting a wide variety of cytokines, chemokines, and growth factors. This can lead to a chronic state of inflammation, and actually support tumor growth. C.) Metabolism. Microbes metabolize dietary intake from the host (fiber, cholesterol, and choline). These are converted into bacterial byproducts, such as short chain fatty acids (SCFAs: butyrate, acetate), lipids, and other metabolites, which modulate host cell behavior. D.) Pathogenic Bacteria. Here, dysbiosis occurs where pathogenic bacteria outcompete commensals by altering the pH and secreting toxins. Some bacteria can attach to the host epithelial layer, or even invade, and induce an immune response. Others actively secrete toxins or possess virulence factors that help break down host tissue and invade further into subsequent layers. The net result is a pro-tumorigenic microenvironment that can promote the progression of cancer.

Figure 3. Summary of Microbial Influence on the Host

A.) Homeostasis. Beneficial bacteria occupy a dominant niche, inhibiting the growth of potentially pathogenic organisms. The integrity of the host organ is maintained and the immune system tolerates and limits bacterial expansion. B.) Barrier Disruption and Inflammation. The barrier integrity of the host organ is compromised, due to tumor growth for example, allowing translocation of bacteria through the barrier, deeper into the organ. This elicits a robust immune response, as immune cells rush into the area, secreting a wide variety of cytokines, chemokines, and growth factors. This can lead to a chronic state of inflammation, and actually support tumor growth. C.) Metabolism. Microbes metabolize dietary intake from the host (fiber, cholesterol, and choline). These are converted into bacterial byproducts, such as short chain fatty acids (SCFAs: butyrate, acetate), lipids, and other metabolites, which modulate host cell behavior. D.) Pathogenic Bacteria. Here, dysbiosis occurs where pathogenic bacteria outcompete commensals by altering the pH and secreting toxins. Some bacteria can attach to the host epithelial layer, or even invade, and induce an immune response. Others actively secrete toxins or possess virulence factors that help break down host tissue and invade further into subsequent layers. The net result is a pro-tumorigenic microenvironment that can promote the progression of cancer.