Intratumoral microbial distribution and tyrosine regulation in head and neck squamous cell carcinoma

The composition of intratumoral microbial communities is cancer-type-specific. However, the role of intratumoral microbes and their regulatory mechanisms in HNSCC remain unclear. This study aimed to investigate the distribution of intratumoral microbes and to explore their correlation with metabolites in HNSCC. Microbial communities in HNSCC and adjacent normal tissues were profiled using 2bRAD sequencing, and differences in metabolite profiles were assessed using non-targeted metabolomic analysis. A total of 285 bacterial genera (864 species) and 11 fungal genera (23 species) were identified across HNSCC tumors and adjacent normal tissues, and 5 genera and 7 species differed significantly between the two groups. Klebsiella pneumoniae was identified as the most important feature distinguishing tumor tissues from adjacent normal tissues. Thirty-three metabolites were differentially expressed between HNSCC tumors and adjacent normal tissues, including 17 downregulated and 16 upregulated metabolites. KEGG pathway analysis identified shared crosstalk pathways between metabolites and microbes, with tyrosine playing a central role. Tyrosine promoted HNSCC cell proliferation and migration via in vitro and in vivo assays. Tyrosine was potentially correlated with Campylobacter rectus and Eikenella corrodens using Spearman's rank correlation analysis. Amino acid metabolism plays a significant role in HNSCC progression and may be modulated by intratumoral microbial communities. Our findings highlight the potential regulatory interactions between specific microbes and metabolites in HNSCC and provide new insights into future research and therapeutic development.