Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans

Prebiotic galacto- and fructo-oligosaccharides (scGOS/lcFOS), resembling oligosaccharides in human milk, have been reported to reduce the development of allergy through modulation of the intestinal microbiota and immune system. Intestinal epithelial cells (IEC) abundantly express galectins, which modulate T cell responses. In particular, galectin-9 (Gal9) has been shown to regulate mast cell degranulation and T cell differentiation. To study the involvement of galectin-9 in food allergy, mice were orally sensitized to whey, while receiving a diet containing Bifidobacterium breve M-16V and scGOS/lcFOS (synbiotics). We found that Gal9 is basolaterally expressed and secreted by IEC, resulting in enhanced Gal9 concentrations in serum, correlating with decreased allergic symptoms. Sera from mice fed synbiotics suppressed ex vivo RBL-2H3 degranulation, which was abrogated by neutralizing Gal9. Furthermore, mice fed synbiotics showed enhanced Th1 and Treg differentiation in mesenteric lymphnodes, which was observed in Gal9 exposed human PBMC cultures as well. In addition, infants suffering from atopic dermatitis receiving synbiotics showed enhanced Gal- 9 levels in serum, which coincided with less severe allergic symptoms. These results indicate that dietary supplementation with synbiotics has significant implications for the prevention of allergy through Gal9 secretion by IEC.