Hidradenitis suppurativa patients exhibit a distinctive and highly individualized skin virome

Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by recurring skin lesions. Despite ongoing research, the exact cause underlying initiation and progression of disease remains unknown. While prior research has linked the skin microbiota to HS pathology, the role of viruses has remained unexplored. To investigate the skin virome, metagenomic sequencing of viral particles was performed on 144 skin samples from 57 individuals (39 HS patients and 18 controls). It was found that the virome is not only linked to BMI, but also to the presence and severity of HS, marking a diverging viral profile in the progression of disease. Despite no differences in alpha-diversity, HS patients exhibited a significantly higher beta-diversity compared to healthy controls, indicating a more personalized virome with reduced viral sharing among patients. We identified distinct groups of commonly shared phages, referred to as the core phageome, associated with either healthy controls or patients. Healthy controls displayed a higher abundance of two core Caudoviricetes phages predicted to infect Corynebacterium and Staphylococcus, comprising normal skin commensals. In contrast, HS patients carried previously uncharacterized phages that were more prevalent in advanced stages of the disease, which likely infect Peptoniphilus and Finegoldia, known HS-associated pathogens. Interestingly, genes involved in superinfection exclusion and antibiotic resistance could be found in phage genomes of healthy controls and HS patients, respectively. In conclusion, we report the existence of distinct core phages that may have clinical relevance in HS pathology by influencing skin bacteria through mechanisms such as superinfection exclusion and antibiotic resistance.IMPORTANCEAn increasing body of research showed that the microbiome has an important role in complex human disease. In line with this, here, we analyzed a longitudinal HS cohort and found a relationship between the skin virome and HS pathology. This relationship was defined by distinct groups of phages associated with either healthy controls or HS patients, yet, in both instances, capable of enhancing bacterial fitness. In healthy individuals, these phages were widely shared, fostering symbiosis by ensuring stability of the commensal skin microbiota. Conversely, in HS patients, these phages revealed a more individualistic nature and could contribute to dysbiosis by providing antibiotic resistance genes to bacterial pathogens. Overall, these findings point to a potential clinical significance of the virome in understanding and addressing HS pathology.