Microbiota and metabolomic profiling coupled with machine learning to identify biomarkers and drug targets in nasopharyngeal carcinoma

Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in certain regions, with radiotherapy as the standard treatment. However, resistance to radiotherapy remains a critical challenge, necessitating the identification of novel biomarkers and therapeutic targets. The tumor-associated microbiota and metabolites have emerged as potential modulators of radiotherapy outcomes. Methods: This study included 22 NPC patients stratified into radiotherapy-responsive (R, n = 12) and radiotherapy-non-responsive (NR, n = 10) groups. Tumor tissue and fecal samples were subjected to 16S rRNA sequencing to profile microbiota composition and targeted metabolomics to quantify short-chain fatty acids (SCFAs). The XGBoost algorithm was applied to identify microbial taxa associated with radiotherapy response, and quantitative PCR (qPCR) was used to validate key findings. Statistical analyses were conducted to assess differences in microbial diversity, relative abundance, and metabolite levels between the groups. Results: Significant differences in alpha diversity at the species level were observed between the R and NR groups. Bacteroides acidifaciens was enriched in the NR group, while Propionibacterium acnes and Clostridium magna were more abundant in the R group. Machine learning identified Acidosoma, Propionibacterium acnes, and Clostridium magna as key predictors of radiotherapy response. Metabolomic profiling revealed elevated acetate levels in the NR group, implicating its role in tumor growth and immune evasion. Validation via qPCR confirmed the differential abundance of these microbial taxa in both tumor tissue and fecal samples. Discussion: Our findings highlight the interplay between microbiota and metabolite profiles in influencing radiotherapy outcomes in NPC. These results suggest that targeting the microbiota-metabolite axis may enhance radiotherapy efficacy in NPC.