Hidradenitis suppurativa skin microbiome: In‐depth analysis and modulation by systemic therapies

Abstract Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial pathogenesis involving genetic, lifestyle and microbial factors. While cutaneous microbiome shifts have been reported for this disease, the impact of systemic immunomodulators and antibiotics on HS microbiome remains poorly defined. Objective To characterize species‐level cutaneous dysbiosis in HS and evaluate the effects of three standard‐of‐care systemic therapies, clindamycin/rifampicin (ATB), adalimumab (ADA) and secukinumab (SEC) on skin microbial composition. Methods We performed 16S rRNA sequencing on 251 skin swabs from lesional and non‐lesional sites of 52 HS patients and 31 healthy matched controls. In a sub‐cohort of 28 patients, microbial shifts were evaluated following 12 weeks of therapy with ATB ( n = 8), ADA ( n = 12) and SEC ( n = 8). Results HS skin exhibited profound dysbiosis defined by the depletion of homeostatic commensals ( Cutibacterium acnes , Staphylococcus hominis , S. epidermidis ) and a synergistic expansion of anaerobic pathogens, primarily Gram‐positive anaerobic cocci (GPAC; Finegoldia magna , Peptoniphilus grossensis and Fenollaria massiliensis ), Lawsonella clevelandensis and Campylobacter ureolyticus . A 13‐taxa microbial signature accurately discriminated the HS phenotype (AUC = 0.92). Following 12 weeks of treatment, ATB markedly attenuated dysbiosis by reducing pathogen loads and significantly increasing microbial richness. In contrast, ADA and SEC did not alter pathogen abundance and were associated with a slight decline in protective commensals. Conclusions Systemic antibiotics partially restore cutaneous microbiome homeostasis in HS by targeting anaerobic pathogens while preserving beneficial commensals, an effect not observed with the tested biologics. These findings highlight the need for microbiome‐directed adjuvant therapies to complement immunomodulation in HS management.