Early-onset colon cancer shows a distinct intestinal microbiome and a host-microbe interaction.

The incidence rate of colorectal cancer (CRC) in younger adults has been rising in developed countries. This trend may be attributed to environmental exposures as a result of lifestyle changes. Many of the lifestyle factors that promote CRC can also affect the gut microbiome, which may be associated with CRC risks. The role of the microbiome in the ongoing rise of early-onset CRC is unknown. Here, we aimed to investigate age-related differences in the gut microbiome of CRC patients and healthy individuals by examining both the fecal and tumor microbiomes. We utilized the publicly accessible data on fecal shotgun metagenomics from CuratedMetagenomeData and The Cancer Genome Atlas (TCGA) via the GDC Data Portal. Comparison of 701 CRC and 693 controls revealed that microbial features were age dependent, with a significant difference in species enrichment between early-onset (<50 years) and late-onset (>65 years) CRC patients. Analysis of the tumor-associated microbiome in a separate dataset of 85 CRC patients verified age-specific differences in taxon abundance between early- and late-onset CRC patients. Finally, using host gene expression data, we found a stronger microbe-host interaction in early- vs. late-onset CRCs. Altogether, these findings indicate that microbial features were age-dependent with stronger microbial-host interactions at the tumor site in early-onset CRCs, suggesting a direct role of microbes in tumorigenesis via interaction with cancer-related pathways in this age-group.