IBD Patients Show a Unique Skin Microbiota Composition and a Correlation Pattern Between Serological Biomarkers and Clinical Aspects During Skin Adverse Events in the Setting of Anti-TNFα Therapy

Abstract

Background Crohn’s disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where gut but not skin dysbiosis is well recognized. Tumor-necrosis factor alpha (TNFα) blockers have been successful in IBD treatment, but up to a quarter of patients suffer from skin adverse events (SkAE), for which we do not have a tool to predict them. Therefore, we examined the skin microbiota composition of IBD patients at several body sites by 16S bacterial profiling. Moreover, we quantified 22 serum markers of inflammation and epithelial barrier disruption in the setting of anti-TNFα therapy and SkAE manifestation by ELISA. Results The skin microbiota signature of IBD patients differed markedly from healthy subjects. In particular, skin microbiota of CD patients differed significantly from that of UC and HC at the retroauricular crease. CD patients showed high abundance of Corynebacterium (ASV86) and lower abundance of Actinomyces (ASV28), Cutibacterium (ASV212), Lawsonella (ASV87), and other taxa compared to HC. UC patients showed higher abundance of Delftia (ASV1039) and Pseudomonas (ASV1183), and lower abundance of Actinomyces (ASV28), Streptococcus (ASV607), or Haemophilus (ASV1150) than HC. Although microbiome changes were correlated at the ASV level in CD and UC patients compared to HC, we identified some bacterial ASV’s that exhibited changes typical of individual IBD forms. Manifestation of SkAE during anti-TNFα therapy was associated with a specific microbiota profile on the skin, and with a decrease in serum levels of L-FABP and I-FABP. Conclusions The overall proinflammatory effect of IBD might predispose for altered skin microbiota composition, hence promoting SkAE manifestation during anti-TNFα therapy. We identified specific serum markers associated with the incidence of SkAE during anti-TNFα therapy, however, further studies are needed to shed light on the impact of microbiota in this matter. Combining sequencing technology with search for serum biomarkers has opened up new opportunities in studying SkAE related to anti-TNFα therapy. Early detection of changes in microbiota-host equilibrium may have beneficial consequences in revealing the pathogenesis of SkAE in IBD.