Immune-microbiota crosstalk in colorectal cancer: mechanistic pathways, biomarkers, and translational therapeutics.

Colorectal cancer (CRC) is caused by a complex interaction between genetic, environmental, and microbial risk factors, and intestinal microbiota has critical roles in inflammation, immunology, and epithelial integrity. Pathobionts from the intestines (Fusobacterium nucleatum, Bacteroides fragilis, and E. coli that produce colibactin) promote DNA damage, immunity protection from cancer therapy, and resistance to chemotherapy treatments. The beneficial commensals and metabolites of intestinal microbes (namely butyrate) increase the mucosal immune response and inhibit tumor-specific signaling mechanisms. Microbe controlled changes of populations of myeloid, lymphoid, and regulatory cells dictate the state of the tumor-immune system and provide actionable checkpoints and biomarkers for cancer therapy. An enormous variety of clinical interventions based on the gut microbiota (probiotics, prebiotics, and fecal microbiota transfer) and diagnostic approaches is currently being developed. Translational issues are difficult due to the interindividual variability and regulatory complexity of tumors. Research needs include standardizing multi-omics data from multidisciplinary teams and mechanistic validation in organoid and gnotobiotic models as well as prediction algorithms to optimize the microbiome-based medicine for individual patients. Targeting the immune-microbiota axis may provide new therapeutic strategies in the diagnosis, prognosis, and therapy of CRC.