The complex interplay between inflammation, the microbiota and colorectal cancer

Abstract

The microbiome has captured the attention of scientists from multiple research fields including ecology, immunology, microbiology and cancer biology. The microbial community living in the gastrointestinal tract is the most abundant and diverse niche of the human body and it is not surprising that microbiome research has predominantly focused upon this organ system. In this addendum, we summarize the latest developments in microbiome research on inflammatory bowel diseases and colorectal cancer. In addition, we highlight our recent findings that chronic intestinal inflammation modulates microbial community composition and the development of colorectal cancer. Our findings redefine the paradigm of inflammation-associated cancer by illuminating the key role of bacteria in development of colorectal cancer.

Keywords: Escherichia coli; bacterial toxin; colibactin; colon cancer; inflammation; microbiome.

Figure 1. Dysbiosis in Il10^−/− mice is driven by inflammation rather than cancer. WT and Il10^−/− mice were transferred from germ-free to specific pathogen free (SPF) conditions. In SPF conditions, WT mice remain healthy, but 100% of Il10^−/− mice develop colitis. Half of each cohort was treated with AOM, which induces no cancer in WT mice but cancer in ~60–80% of Il10^−/− mice. When the microbiota of each cohort was assessed by Illumina sequencing of 16S ribosomal genes, we found it did not differ by cancer status (Il10^−/− vs. AOM/Il10^−/−). In contrast, inflammatory status (Il10^−/− vs. WT) was associated with alterations in microbial community composition, including an expansion of Enterobacteriaceae bacteria.

Figure 2. Model for enhanced tumorigenicity by pks+ E. coli.