Specific non-digestible oligosaccharides combined with B. Breve M-16V attenuates experimental colitis and suppress Th17 immunity potentially via regulation of galectin-4 and-9 expression in the gut

Background: Dietary intervention using short-chain galacto- and long-chain fructo-oligosaccharides (GF) in combination with Bifidobacterium breve M-16V (GF/Bb) is known to support the induction of Treg cells. We addressed whether dextran sodium sulfate (DSS)- induced colitis can be attenuated by dietary supplementation with GF/Bb and hypothesized a possible involvement of galectins in IBD. Methods: The murine DSS colitis model was utilized to study the effects of dietary supplementation with Bb, GF and GF/Bb on development of colitis. Epithelial galectin-4 and -9 expression as well as dendritic cell (DC) activation and T cell polarization in gut-associated lymphoid tissue (GALT) were analyzed. Galectin- 4 and -9 expression were also analyzed in human surgical resection specimens from UC and CD patients. Results: DSS-induced colitis in the mouse is associated with increased galectin-4 and reduced galectin-9 expression in colon and small intestine, respectively. Similarly, in inflamed UC and CD tissue, increased galectin-4 and reduced galectin-9 expression in the intestinal epithelium was observed. Dietary supplementation with Bb or GF/Bb attenuated murine colitis and ameliorated DSS-elevated intestinal galectin-4 levels whilst restoring galectin-9 levels. GF/Bb most effectively reduced DC activation and increased the frequency of CD103+ tolerogenic DC in mesenteric lymph nodes. GF/Bb treatment decreased the frequency of activated T cells as well as Th17 and Th1 cells in GALT, while Treg cell frequency was enhanced. Conclusions: GF/Bb attenuates the development of DSS-induced intestinal inflammation, suppresses epithelial galectin-4 expression and supports Treg conversion while suppressing Th1 and Th17 cells in GALT.