Fiber-Associated Lachnospiraceae Reduce Colon Tumorigenesis by Modulation of the Tumor-Immune Microenvironment

Despite increasing evidence implicating the gut microbiome in CRC, the collective role of different microbial consortia in CRC carcinogenesis is unclear. We have previously described these consortia as co-abundance groups that co-exist at different abundance levels in the same patient. Here, we report that tumor biopsy tissue from patients with a “high-risk” Pathogen-type microbiome had a different immune transcriptome and immune cell infiltrate from those with a “low-risk” Lachnospiraceae-type microbiome. Transplantation from patients of the two fecal microbiome types into mice with an orthotopic tumor differentially affected tumor growth and the systemic anti-tumor immune response, which correlated with differences in the engrafted human microbial species and predicted microbiome-encoded metabolites in the two groups. These data suggest that the enrichment for a Lachnospiraceae-type configuration of the gut microbiome may influence colon cancer progression and disease outcome by modulating the local and systemic anti-tumor immune response.