Roseburia intestinalis Modulates Immune Responses by Inducing M1 Macrophage Polarization

Abstract

In recent years, the gut microbiome has been recognized as one influential factor in cancer development. Particularly in colorectal cancer (CRC), several studies observed a major imbalance of the intestinal microbiota, marked by a reduction in beneficial bacterial species, such as Roseburia intestinalis, and an increase in opportunistic pathobionts, like Peptostreptococcus stomatis. We previously observed that specific Eubacteriales, including R. intestinalis, were significantly reduced in CRC patients and have a potent anti-tumor immune effect when applied as oral monotherapy in mice. Here, we investigate the molecular mechanism of R. intestinalis on various cell types in vitro, highlighting its potential therapeutic value in CRC. Co-culture experiments with macrophages demonstrated that R. intestinalis exposure induced an increase in the M1 phenotype and decreased the M2 phenotype, suggesting macrophage-polarizing properties of these bacteria. R. intestinalis also triggered a gene expression profile resembling M1 macrophages and led to distinct chemokine and cytokine secretion in cancer cells, suggesting an immune-activating environment. However, we did not observe direct cytotoxic effects in cancer cells. Our research provides insights into the potential of R. intestinalis to activate immune responses, supporting further investigation into its therapeutic role in CRC. These findings underscore the need for deeper studies on the bacterium’s impact on CRC pathogenesis and treatment.