Cytokine Toxicity and Bacterial Dysbiosis in Chemotherapy- and/or Radiotherapy-Induced Oral Mucositis: Pathophysiological Mechanisms and Therapeutic Interventions

Chemotherapy- and/or radiotherapy-induced oral mucositis (CRIOM) is a common and debilitating complication in patients with head and neck cancer, driven largely by excessive proinflammatory cytokine signalling and treatment-associated bacterial dysbiosis. This review synthesizes current mechanistic evidence on cytokine toxicity and microbial imbalance in pathogenesis of CRIOM and to summarize emerging therapeutic strategies targeting these pathways. A structured PubMed search identified preclinical and clinical studies evaluating cytokine-mediated inflammation, microbiome alterations, and interventions with anti-inflammatory or microbiota-modulating effects. The reviewed evidence demonstrates that elevated IL-1β, IL-6, TNF-α, iNOS, and nitric oxide amplify tissue injury and ulceration, while disruption of oral and gut microbial communities, characterized by loss of beneficial commensals and enrichment of pathogenic taxa, further exacerbates mucosal inflammation. Anti-inflammatory agents, including pentoxifylline, atorvastatin, trans-caryophyllene, azilsartan, recombinant human IL-11, and low-level laser therapy reduced cytokine levels and improved mucosal healing. Additionally, microbiome-targeted approaches such as oral microbiota transplantation and a multi-strain probiotic cocktail restored microbial balance and attenuated CRIOM severity. Overall, current findings highlight cytokine toxicity and dysbiosis as synergistic drivers of CRIOM and support anti-inflammatory and microbiome-modulating therapies as promising adjunctive strategies; however, further studies incorporating patient-specific factors is needed to guide optimized clinical application.