Microbiome-targeted therapeutics in head & neck cancer.

The oral microbiome is increasingly recognized as a critical factor in the development, progression, and response to therapy of head and neck cancer. Microbial dysbiosis has been associated with chronic inflammation, immune modulation, altered cellular proliferation and apoptosis, and the production of carcinogenic metabolites which collectively shape the tumor microenvironment. Various bacterial species, including Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus mutans, and Treponema denticola, as well as fungal species such as Candida albicans and non-albicans Candida, have been implicated in oral carcinogenesis. These microorganisms promote tumorigenic processes through the generation of carcinogens such as nitrosamines and acetaldehyde, which activate innate immune pathways such as nuclear factor kappa B and Wnt/β-catenin. Conversely, several commensal species, including Neisseriaceae, Kingella, Corynebacterium, Prevotella nanceiensis, Capnocytophaga leadbetteri, and Selenomonas sputigena, have been associated with a reduced prevalence of head and neck cancer, suggesting a potential association between microbial homeostasis and reduced cancer risk. Advances in microbiome research have led to the exploration of microbiome-targeted therapeutic strategies as adjuncts to conventional head and neck cancer treatment. Approaches including probiotics, prebiotics, postbiotics, dietary modulation, and fecal microbiota transplantation aim to restore microbial balance, enhance antitumor immune responses, mitigate therapy-induced toxicities, and improve treatment efficacy. Probiotic formulations containing Lactobacillus and Bifidobacterium species have shown promise in reducing adverse effects and improving patient quality of life and treatment adherence. This chapter summarizes current evidence on microbiome dysbiosis in head and neck cancer and reviews emerging microbiome-targeted interventions with potential clinical relevance.