Gut microbiome profiles as predictors of response to chemoradiotherapy in locally advanced rectal cancer

This prospective cohort study investigates the predictive role of gut microbiota composition in determining the therapeutic response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) at Qiqihar Jianhua Hospital. A total of 178 patients underwent standardized CRT protocols and were stratified into responders and non-responders based on pathological tumor regression grades. Gut microbiome profiling was conducted via 16S rRNA amplicon sequencing and shotgun metagenomics at three treatment stages (pre-, mid-, and post-CRT). Responders exhibited significantly higher alpha diversity (Shannon, Chao1) at baseline and maintained greater microbial richness throughout treatment. Taxonomic analysis identified Faecalibacterium, Akkermansia, and Bifidobacterium as enriched in responders, while non-responders showed elevated Clostridium, Escherichia, and Streptococcus. Multivariate regression confirmed Faecalibacterium (OR = 1.16, P = 0.0002) and Akkermansia (OR = 1.27, P = 0.0146) as independent predictors of CRT response. Functional profiling revealed enrichment of anti-inflammatory pathways (butyrate synthesis, tryptophan metabolism) in responders and pro-inflammatory, stress-related functions (lipopolysaccharide biosynthesis, oxidative stress) in non-responders. Exploratory microbiome modulation using probiotics or fecal microbiota transplantation (FMT) targeting Faecalibacterium and Akkermansia demonstrated increased responder rates by 12.5 and 18.2%, respectively. These findings highlight the potential of gut microbiome signatures as non-invasive biomarkers for CRT response prediction and as targets for adjunctive therapeutic strategies. Personalized microbiome-informed treatment may enhance CRT efficacy and reduce unnecessary exposure in non-responders, paving the way for precision oncology in rectal cancer.