Konstantinos Petalas, George Ν. Konstantinou
Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disease of the nasal and paranasal sinus mucosa with substantial impact on quality of life. Although atopy and/or allergic rhinitis frequently coexist with CRS, often alongside type 2-skewed inflammation, the extent to which allergic mechanisms define a discrete CRS entity remains debated, in part due to inconsistent operational definitions and overlapping clinical phenotypes. In parallel, culture-independent sequencing studies have reframed CRS as a disorder of host–microbe interactions, with many cohorts reporting reduced sinonasal microbial diversity, enrichment of potentially pathogen taxa (including Staphylococcus aureus), and biofilm-associated community states. However, causality and directionality remain uncertain. In this narrative review, we synthesize evidence at the interface of epithelial barrier dysfunction, type 2 cytokine networks (IL-4/IL-13/IL-5), and microbiome dysbiosis, highlighting where data are consistent across studies versus where findings are heterogeneous or predominantly associative. We discuss representative allergy-associated CRS prototypes such as allergic fungal rhinosinusitis and central compartment atopic disease as clinical models to interrogate these interactions, while distinguishing them from non–IgE-mediated type 2 entities such as aspirin-exacerbated respiratory disease. We also summarize current data linking atopy to sinonasal microbial signatures and discuss emerging microbiome-directed interventions (topical probiotics, bacteriophages, and microbiota transfer concepts) alongside biologics and precision anti-inflammatory therapies. Finally, we highlight key knowledge gaps, including the limited endotype-resolved and longitudinal studies, variable allergic phenotyping in microbiome research, and the need for standardized definitions and biomarker-driven stratification to clarify clinical utility and to guide mechanism-informed therapeutic trials.