Dietary intervention with synbiotics protects against allergic disease via induction of galectin-9 by intestinal epithelial cells

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 (Gal9), induced by a specific oligosaccharide mixture of short chain galacto- and long chain fructooligosaccharide (scGOS/lcFOS) and TLR9 ligand and its relevance for the suppression of allergic disease were determined both in vitro and in vivo. Human IEC were exposed to scGOS/lcFOS together with TLR ligands, cocultured with PBMC and cytokines and immune cell phenotype were measured. In vivo, mice were sensitized orally to whey, fed a diet containing Bifidobacterium breve M-16V and scGOS/lcFOS (GF/Bb). Gal9 expression was determined by immunohistochemistry and by ELISA. In addition, in a double-blind, placebo-controlled multicentre trial, Gal9 levels were measured in sera of 90 infants with atopic dermatitis that received hydrolysed formulae with or without GF/Bb for 12 weeks. Apical exposure of IEC to scGOS/lcFOS and TLR9 ligand or genomic DNA from Bb M-16V enhanced IFN-γ secretion by co-cultured PBMC and resulted in increased percentages of Th1 and Treg cells. The expression and secretion of IEC-derived Gal9 increased after combined addition of scGOS/ lcFOS and TLR9 ligand. Furthermore, development of Th1 and Treg cells was enhanced in Gal9 treated PBMC, resulting in increased IL-10 and IFN-γ, but suppressed IL-17. In vivo, the GF/Bb diet resulted in reduced acute ear swelling response upon dermal challenge with allergen and lower serum mMCP-1. Furthermore, the GF/Bb diet enhanced serum Gal9 levels, which correlated with decreased allergic symptoms and immunohistochemistry revealed specific basolateral Gal9 expression on IEC. In addition, infants suffering from atopic dermatitis receiving the GF/Bb diet also showed enhanced Gal-9 levels in serum, which coincided with less severe allergic symptoms. These data indicate that dietary supplementation with scGOS/lcFOS has significant implications for the prevention of allergy through TLR9-induced Gal9 secretion by IEC.