Fiber-associated Lachnospiraceae reduce colon tumorigenesis by modulation of the tumor-immune microenvironment

Abstract Several studies have highlighted the role of the gut microbiota in colorectal cancer (CRC) progression. Patients with CRC harbor gut microbiomes that differ in structure and function from those of healthy individuals, suggesting this altered microbiome could contribute to carcinogenesis. Despite the increasing evidence implicating the gut microbiome in CRC, the collective role of different microbial consortia in CRC carcinogenesis is unclear. Using a combination of 16S rRNA amplicon sequencing, transcriptomics, and metagenomics, we assessed the capacity of the gut microbiota to shape the tumor microbiome, modulate the immune system and, ultimately, affect tumor growth. Here, we found that tumor biopsy tissue from patients with a “high-risk” Pathogen-type microbiome had a different immune transcriptome 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. The differences in tumor volume and immunophenotype between mice receiving the high-risk and the low-risk microbiome correlated with differences in the engrafted human microbial species and predicted microbiome-encoded metabolites in the two groups. These data suggest that the configuration of the gut microbiome may influence colon cancer progression and disease outcome by modulating the anti-tumor immune response.