Characterization of the skin microbiota in bullous pemphigoid patients and controls reveals novel microbial indicators of disease

• Published in: Journal of advanced research 2023-02, Vol.44, p.71-79
• Main Authors: Belheouane, Meriem, Hermes, Britt M., Van Beek, Nina, Benoit, Sandrine, Bernard, Philippe, Drenovska, Kossara, Gerdes, Sascha, Gläser, Regine, Goebeler, Matthias, Günther, Claudia, von Georg, Anabelle, Hammers, Christoph M., Holtsche, Maike M., Homey, Bernhard, Horváth, Orsolya N., Hübner, Franziska, Linnemann, Beke, Joly, Pascal, Márton, Dalma, Patsatsi, Aikaterini, Pföhler, Claudia, Sárdy, Miklós, Huilaja, Laura, Vassileva, Snejina, Zillikens, Detlef, Ibrahim, Saleh, Sadik, Christian D., Schmidt, Enno, Baines, John F.
• Format: Article
• Language: English
• Subjects: 16s rRNA gene sequencing; Aged; Autoimmune blistering disease; Autoimmune Diseases - pathology; Blister - pathology; Bullous pemphigoid; Humans; Microbiota; Original; Pemphigoid, Bullous - pathology; Pemphigoid, Bullous - therapy; Risk factor; Skin; Skin microbiota
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2022.03.019

[Display omitted] •We conducted a large-scale investigation of skin microbiota composition and diversity in BP.•We reveal substantial differences in skin microbiota in patients with BP compared to that of control subjects.•We observe a transitional stage between normal- and diseased skin within patients with BP.•BP is characterized by a loss of protective microbiota and an increase in S. aureus, an inflammation-promoting species.•S. aureus ubiquitously associates with BP, suggesting a role in pathogenesis.•Our results may help inform clinical markers for assessing BP disease risk and prognosis. Bullous pemphigoid (BP) is the most common autoimmune blistering disease. It predominately afflicts the elderly and is significantly associated with increased mortality. The observation of age-dependent changes in the skin microbiota as well as its involvement in other inflammatory skin disorders suggests that skin microbiota may play a role in the emergence of BP blistering. We hypothesize that changes in microbial diversity associated with BP might occur before the emergence of disease lesions, and thus could represent an early indicator of blistering risk. The present study aims to investigate potential relationships between skin microbiota and BP and elaborate on important changes in microbial diversity associated with blistering in BP. The study consisted of an extensive sampling effort of the skin microbiota in patients with BP and age- and sex-matched controls to analyze whether intra-individual, body site, and/or geographical variation correlate with changes in skin microbial composition in BP and/or blistering status. We find significant differences in the skin microbiota of patients with BP compared to that of controls, and moreover that disease status rather than skin biogeography (body site) governs skin microbiota composition in patients with BP. Our data reveal a discernible transition between normal skin and the skin surrounding BP lesions, which is characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, Staphylococcus aureus is ubiquitously associated with BP disease status, regardless of the presence of blisters. The present study suggests Staphylococcus aureus may be a key taxon associated with BP disease status. Importantly, we however find contrasting patterns in the relative abundances of Staphylococcus hominis and Staphylococcus aureus reliabl