Mapping the microbiota in hidradenitis suppurativa

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McCarthy, Siobhán
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University College Cork
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistula at intertriginous sites. Pain, pruritus, malodour, and suppuration have a significant impact on quality of life for HS patients. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. Skin microbiome alterations in HS have become an area of expanding research with its role in the pathogenesis of HS becoming clearer. Gut microbiome alterations have been described in many inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, and cancer, but little is known about the gut microbiome in HS. Our hypothesis is that gut, as well as skin, microbiota alterations and their metabolites, may be responsible for skin inflammation in HS. The level of pain experienced by 150 patients with HS was measured using the visual analogue scale and EQ-5D-5L questionnaires. 59 patients with HS provided faecal samples, nasal and skin swabs of affected sites for analysis. These 59 patients also provided serum samples and completed questionnaires including the Dermatology Life Quality Index (DLQI), Morisky Medication Adherence Scale, International Physical Activity Questionnaire, and Food Frequency Questionnaire. 30 healthy controls provided fecal samples and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S rRNA gene amplicon sequencing on total DNA derived from the samples. Calprotectin was determined by enzyme-linked immunoassay (CALPROLAB™ Calprotectin ELISA (HRP). Complement C5a levels were assessed using enzyme-linked immunosorbent assay (Abcam ab193695 Complement C5a Human ELISA Kit). Pain was widely reported in 134 responders to the visual analog scale questionnaire. 82.1% reported some level of pain and 35.8% reported high levels of pain. In the EQ-5D-5L questionnaire, 81.4% of responders indicated that they felt pain or discomfort, and 31.0% expressed “severe” or “extreme” pain/discomfort. Weak correlation was seen between levels of pain and one marker of gut microbiota alpha diversity (Chao1), but this failed to be repeated for all indices of microbiota species richness. A significant impact on quality of life with a mean DLQI score of 12.15 (SD 7.67) was observed in patients with HS, which is in line with other severe dermatoses. 59% of patients reported a large or extremely large impact on their quality of life. The DLQI score did not correlate with gut microbial diversity. In this study, over 40% of patients with HS also reported some difficulty remembering to take their medications with 20% reporting that they forgot to take their medication in the previous 2 weeks. Patients with HS also reported moderate-to-high levels of physical activity; however this may be overestimated. Alterations in gut microbiota diversity did not correlate with levels of physical activity. Microbiome alpha diversity was significantly lower in the faecal, skin and nasal samples of individuals with HS which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the faecal microbiome of individuals with HS, which is also reported in Crohn’s disease (CD), suggesting comorbidity due to shared gut microbiota alterations. No significant difference in faecal microbiota composition or overall habitual diet was seen in the patients with HS and diet was not associated with disease severity. Diet in HS was significantly different to controls, and similar to patients with CD. Finegoldia magna was over-abundant in HS skin samples relative to healthy controls. It is possible local inflammation is driven by F. magna through promoting the formation of neutrophil extracellular traps (NETs). 27.1% of patients with HS had a raised faecal calprotectin level of >50mg/kg with markedly elevated levels of >150mg/kg in 8.5% suggesting occult gastrointestinal inflammation. Median complement C5a level in patients with HS was elevated at 47 ng/ml (IQR 30.55 ng/ml) which is in keeping with prior studies. These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies including faecal microbiota transplant or bacteriotherapy could be of benefit. Faecal calprotectin is a simple test which should be considered in patients with HS, with further investigations warranted in patients with elevated levels. C5a may provide a therapeutic target in patients with HS and serum C5a may act a biomarker of the disease.
Hidradenitis suppurativa , Gut microbiota , Skin microbiota
McCarthy, S. M. 2022. Mapping the microbiota in hidradenitis suppurativa. PhD Thesis, University College Cork.