Abstract
Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.
Highlights
Inflammatory bowel diseases (IBD) affect up to seven million people globally and three million in Europe and their incidence and prevalence are increasing [1,2]
As mucosa-associated microbiota dysbiosis could be more obvious and relevant for inflammation, we focused in this study on the mucosa-associated microbiota of Finnish pediatric patients with ulcerative colitis (UC, n = 26) and non-IBD subjects as controls
We carried out high-throughput sequencing of the microbiota and applied a targeted host gene expression analysis to study mucosal microbiota–host interactions in Finnish pediatric UC patients and controls
Summary
Inflammatory bowel diseases (IBD) affect up to seven million people globally and three million in Europe and their incidence and prevalence are increasing [1,2]. The majority of the IBD-associated genes code for immunological and epithelial barrier functions, which direct the hosts response to environmental factors and determine mucosal homeostasis [3]. Both omics-based and targeted analysis of gene expression in the intestinal epithelium have revealed IBD-associated alterations, which were independent from inflammation status [4,5]. Antimicrobial peptides (AMPs), including α- and β-defensins, C type lectins, cathelicidins and S100 proteins, are widely produced as a defense mechanism by intestinal epithelial cells to regulate and maintain homeostasis between the microbiota and the host epithelium [6]. The expression of AMPs by small intestinal Paneth cells, mainly α-defensins, is altered in ileal CD resulting in reduced antimicrobial activity, whereas in UC the colonic antimicrobial barrier, formed by a mucus layer retaining the AMPs, is impaired despite the upregulated epithelial peptide production [6,7]
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