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P025. Reduced Butyricicoccus pulli-caecorum levels in mucosa of UC patients correlate with aberrant CLDN1 expression

S. Devriese1, V. Eeckhaut2, F. Van Immerseel2, R. Ducatelle2, M. De Vos1, D. Laukens1, 1Ghent University, Department of Gastroenterology, Gent, Belgium, 2Ghent University, Department of Pathology, Bacteriology and Avian Diseases, Merelbeke, Belgium

Background

Butyrate maintains colonic homeostasis by modulating a wide variety of cellular functions including the control of intestinal epithelial integrity. Butyrici-coccus pulli-caecorum is a butyrate-producing bacterial strain that is found in reduced amounts in stool samples of patients with ulcerative colitis (UC) and is currently being investigated as a pharmabiotic. Conditioned growth medium of B. pulli-caecorum reduces TNF-induced colonic epithelial permeability in vitro, however its in vivo relevance is unknown. The aim of our research was to investigate the relationship between the presence of B. pulli-caecorum in the colonic mucosa and the expression of tight junction protein 1 (TJP1), occludin (OCLN) and claudin 1 (CLDN1), essential components of the tight junction complex which are partially regulated by butyrate.

Methods

The expression of these genes was analyzed by quantitative real-time PCR (qPCR) in a collection of colonic biopsies from healthy controls (N = 21) and UC patients with active disease (N = 26). Next, the effect of the conditioned growth medium of B. pulli-caecorum (strain 25–3T) on the expression of these genes was investigated in HT-29 cells in the presence or absence of TNF. Finally, B. pulli-caecorum bacteria were quantified in an extended cohort of colonic mucosa of UC patients (N = 36) and healthy controls (N = 31) using a genus-specific qPCR.

Results

TJP1 and OCLN were significantly downregulated in colonic biopsies of UC patients (both P < 0.005), whereas CLDN1 expression was increased (P < 0.003). The conditioned growth medium of B. pulli-caecorum increased the baseline expression of TJP1 and OCLN but did not decrease CLDN1 levels in HT-29 cells. TNF did not affect expression of TJP1 or OCLN but increased CLDN1 expression which was counteracted by 21% after co-incubation with the conditioned growth medium. B. pulli-caecorum could be detected in colonic biopsies of 71% of healthy controls and in only 42% of UC patients (Fisher exact P = 0.026). In addition, in samples where B. pulli-caecorum was detected, the absolute amount was lower in UC samples (P = 0.081). Interestingly, the quantity of B. pulli-caecorum correlated with the deregulated expression of CLDN1 (R = −0.528).

Conclusion

Butyricicoccus pulli-caecorum is a mucus-adherent bacterium and is underrepresented in colonic biopsies of UC patients. Their reduced prevalence correlates with aberrant CLDN1 expression which can be reversed in vitro by the conditioned growth medium of B. pulli-caecorum. Together, these data support a role for B. pulli-caecorum in the preservation of colonic barrier integrity.