The sinonasal microbiome, host defense peptides, and cancer risk: Decoding the immune system’s dilemma in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a prevalent and debilitating condition characterized by persistent inflammation of the sinonasal mucosa. Despite advances in understanding its pathophysiology, the role of microbial communities and their interactions with the host immune system remains poorly understood. This review aims to elucidate the complex interplay between microbial dysbiosis, host immune responses, the dysregulated, cancer-like behavior of inflamed sinus tissue, and the production of antimicrobial peptides (AMPs) and lipids in CRS. A systematic literature review was conducted across databases such as PubMed, Scopus, and Web of Science. Keywords included “chronic rhinosinusitis,” “microbial interactions,” “antimicrobial peptides,” “antimicrobial lipids,” and “immune system.” Studies published between 2020 and 2025 were included, focusing on microbial–immune interactions, AMPs, and lipids in CRS. Data were synthesized to identify key mechanisms and therapeutic implications. Microbial dysbiosis in CRS is associated with altered immune responses and impaired production of AMPs and lipids. Studies demonstrate that microbial interactions can either exacerbate or mitigate inflammation, depending on the balance between pathogenic and commensal species. Immune system dysregulation, particularly in T-cell responses and cytokine production, further exacerbates chronic inflammation. Emerging therapies, such as probiotics and AMP-based treatments, show promise in restoring microbial-immune balance. Future research should focus on developing targeted therapies that restore microbial balance and enhance innate immune defenses. Understanding the role of microbial interactions in CRS offers new avenues for personalized treatment strategies, potentially improving outcomes for patients with this challenging condition.