Reduced Mucosa-associated Butyricicoccus Activity in Patients with Ulcerative Colitis Correlates with Aberrant Claudin-1 Expression.

Abstract

Butyricicoccus is a butyrate-producing clostridial cluster IV genus whose numbers are reduced in the stool of ulcerative colitis [UC] patients. Conditioned medium of Butyricicoccus [B.] pullicaecorum prevents tumour necrosis factor alpha [TNFα]-induced increase in epithelial permeability in vitro. Since butyrate influences intestinal barrier integrity, we further investigated the relationship between the abundance of mucosa-associated Butyricicoccus and the expression of butyrate-regulated tight junction [TJ] genes. Tight junction protein 1 [TJP1], occludin [OCLN], claudin-1 [CLDN1], and Butyricicoccus 16S rRNA expression was analysed in a collection of colonic biopsies of healthy controls and UC patients with active disease. The effect of butyrate and B. pullicaecorum conditioned medium on TJ gene expression was investigated in TNFα-stimulated Caco-2 monolayers and inflamed mucosal biopsies of UC patients. TJP1 expression was significantly decreased in inflamed UC mucosa, whereas CLDN1 mRNA levels were increased. OCLN did not differ significantly between the groups. Mucosa-associated Butyricicoccus 16S rRNA transcripts were reduced in active UC patients compared with healthy controls. Interestingly, Butyricicoccus activity negatively correlated with CLDN1 expression. Butyrate reversed the inflammation-induced increase of CLDN1 protein levels, and stimulation of inflamed UC biopsies with B. pullicaecorum conditioned medium normalized CLDN1 mRNA levels. Butyricicoccus is a mucosa-associated bacterial genus under-represented in colonic mucosa of patients with active UC, whose activity inversely correlates with CLDN1 expression. Butyrate and B. pullicaecorum conditioned medium reduce CLDN1 expression, supporting its use as a pharmabiotic preserving epithelial TJ integrity.