Metabolic Products of Gut Bacteria Influence Tumor Progression and Immune Modulation

Abstract

A healthy composition of the gut microbiome is directly linked to the proper functioning of various systems in the body, most notably the immune system. An increasing number of efforts have been made in modulating the gut microbiome to improve the efficacy of cancer therapy. Indeed, specific bacterial strains correlated in abundance with an enhanced immune response have been identified, with the molecular mechanisms pointing to metabolic products secreted by these bacteria. In this senior thesis, I identify the phenotypes expressed by murine melanoma cells and CD8+ T cells when cultured in vitro with the products of bacteria associated with good and poor responses to immunotherapy. Through a variety of cross-validating methods, I found that products of Bacteroides cellulosilyticus increase the antitumor abilities of immune cells, while products of Phocaeicola vulgatus and Faecalibacterium prausnitzii confer an anti-inflammatory effect. These conclusions pave the way for further study in identifying the specific metabolites responsible, as well as systems-level in vivo studies that explore the complex crosstalk between tumor, immune system, and gut microbiome. A future in which cancer therapy includes a calculated modulation of the gut microbiome to significantly improve prognosis remains a promising possibility.