Microbe-Host Interaction in Rosacea and Its Modulation through Topical Ivermectin

Rosacea is characterized by inflammatory lesions, often accompanied by an increased density of the common skin mite Demodex folliculorum. Although rosacea shows a high prevalence and significantly affects the QOL of patients, the underlying mechanisms, especially the role of cutaneous dysbiosis, are largely unknown. Hence, we aimed to systematically characterize disease severity of patients with rosacea in the context of mite density, the cutaneous microbiome, and the host's transcriptome before and after 30 days of topical 1% ivermectin cream treatment. At day 30, a marked decrease in mite density was observed in 87.5% of patients. At day 0, distinct microbial community changes included the decrease in Cutibacterium acnes abundance, whereas Staphylococcus epidermidis colonization increased compared with that in healthy volunteers. Interestingly, the insect symbiont Snodgrassella alvi was recovered from a highly Demodex-colonized patient and eradicated by treatment on day 30. Although topical ivermectin did not affect bacterial dysbiosis, the host's transcriptome significantly normalized, and an "ivermectin transcriptomic signature" was defined. Findings of this study support that rosacea lesions are associated with dysbiosis. However, improvement of clinical signs during topical ivermectin is not associated with normalization of the bacterial microbiome but rather a decrease of transcriptomic dysregulation and mite density.