Research progress on gut microbiota in colorectal cancer immunotherapy.

Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical benefits in treating various malignancies. However, their therapeutic efficacy exhibits considerable interindividual variability in patients with colorectal cancer (CRC). In recent years, growing attention has been focused on the regulatory role of the gut microbiota and its metabolic microenvironment in modulating ICIs responses. This article systematically reviews key advances in understanding how the gut microbiota and its metabolites influence ICIs efficacy. For example: Specific bacterial species (e.g., Lactobacillus paracasei and Fusobacterium nucleatum) may regulate ICIs efficacy by modulating antigen presentation or the tumor immune microenvironment. Microbial metabolites, such as short-chain fatty acids (SCFAs), can enhance immune function and thereby improve ICIs outcomes. Potential microbiome-targeted interventions-including probiotic/prebiotic combinations, optimized antibiotic administration timing, refined fecal microbiota transplantation (FMT) protocols, and engineered synthetic biology-based bacterial therapies-are also discussed. By synthesizing current evidence, this review provides a theoretical foundation for developing novel personalized immunotherapy strategies for CRC, with a focus on microbiome modulation to optimize ICIs treatment efficacy.