Microbial (bacterial, fungal, and viral) disruptions can cause or contribute to sinus inammation [53–57]. Specic members of the sinonasal microbiome, like S. aureus, can drive maladaptive type 2 inammation in the sinus mucosa via direct superantigen stimulation of T lymphocytes [58], intracellular infection of immune cells [59, 60], superantigen-specic IgE production [61], epithelial barrier disrup­tions [62], and biolm formation [60, 63, 64]. When comparing the microbiome composition (i.e., the genetic material derived from the microbiota of a specic site) of CRS patients to healthy controls, diseased individuals have a lower microbiome diversity compared to healthy subjects [65–68]. Similarly, CRS patients experience more epithelial barrier disruptions when their sinonasal microbiome is less diverse [69]. Microbiota-altering therapies, like fecal microbiota transplantation, can suc­cessfully displace pathogens (80–94% cure rate for Clostridioides difcile) [58, 59] and effectively treat inammatory diseases like ulcerative colitis [70] and atopic dermatitis [71]. We believe that a similar treatment strategy can treat rCRS patients who primarily fail due to biolm formation and colonization by resistant bacterial strains.