Dietary non-digestible oligosaccharide-induced galectin-9 correlates with protection against allergic symptoms

Background: Intestinal epithelial cells (IEC) abundantly express galectins, which are known to modulate T cell responses. In this study, immune modulation and epithelial expression of galectin-9 (Gal-9), induced by a galacto/fructooligosaccharide mixture (scGOS/ lcFOS) and TLR9 ligand, and its relevance for suppression of allergy were determined. Methods: Human IEC were grown on transwell inserts and apically exposed to 0.5% scGOS/lcFOS with TLR9 ligand ans cocultured with activated healthy donor PBMC. Cytokines and immune cell phenotype were measured. In vivo, mice were sensitized orally to whey, while being fed a diet containing Bifidobacterium breve M-16 V and scGOS/lcFOS (GF/Bb). Gal-9 expression was determined by immunohistochemistry in the intestine and measured in serum. In addition, in a double-blind, placebo-controlled multicentre trial, Gal-9 levels were measured in sera of 90 infants with atopic dermatitis receiving hydrolyzed formulae with or without GF/Bb for 12 weeks. Results: IEC-derived Gal-9 mRNA, protein expression, and basolateral secretion increased after combined addition of scGOS/ lcFOS and TLR9 ligand in the co-culture model. This coincided with enhanced IL-10 and IFN-γ secretion by PBMC and increased percentages of Th1 and Treg cells. Basolateral neutralization of galectins suppressed IL-10 and IFN-γ, but enhanced IL-6, IL-17 and TNF-α secretion. Furthermore, development of Th1 and Treg cells was enhanced in Gal-9-treated PBMC dose dependently, resulting in increased IL-10 and IFN-γ, but suppressed IL-17 secretion. Immunohistochemistry in mouse intestine revealed expression of Gal-9 in epithelial cells in the small intestine. Interestingly, the GF/Bb diet enhanced serum Gal-9 levels, which correlated with decreased allergic symptoms. In addition, infants suffering from atopic dermatitis receiving GF/Bb also showed enhanced Gal-9 levels in serum, correlating with less severe allergic symptoms. Conclusion: GF/Bb-induced Gal-9 expression by IEC may protect against the development of allergy via modulating the effector T cell response.