Gut microbiome's causal role in head and neck cancer: findings from mendelian randomization.

Introduction: The gut microbiome (GM) has been implicated in cancer pathogenesis and treatment, including head and neck cancers (HNC). However, the specific microbial compositions influencing HNC and the underlying mechanisms remain largely unknown. Methods: This study utilized published genome-wide association studies (GWAS) summary data-based two-sample Mendelian randomization (MR) to uncover the GM compositions that exert significant causal effects on HNC. Functional annotation and enrichment analysis were conducted to better understand the significant genetic variables and their connection with HNC. The HNC dataset included 2,281 cases and 314,193 controls. The GM GWAS data of 211 gut taxa (35 families, 20 orders, 16 classes, 9 phyla, and 131 genera) were obtained from the MibioGen consortium, involving 18,340 participants. Results: MR analysis revealed four GM compositions exerting causal effects on HNC. Specifically, Conclusions: Our study demonstrates, for the first time, the causal influence of specific gut microbiome compositions on HNC, offering significant insights for advancing clinical research and personalized treatments. The identified GMs may serve as potential biomarkers or therapeutic targets, paving the way for innovative approaches in HNC diagnosis, prevention, and therapy.