Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans.
BACKGROUND
Prebiotic galacto- and fructo-oligosaccharides (scGOS/lcFOS) resembling non-digestible oligosaccharides in human milk reduce the development of atopic disorders. However, the underlying mechanisms are still unclear. Galectins are soluble-type lectins recognizing β-galactoside containing glycans. Galectin-9 has been shown to regulate mast cell degranulation and T-cell differentiation. In this study, the involvement of galectin-9 as a mechanism by which scGOS/lcFOS in combination with Bifidobacterium breve M-16V protects against acute allergic symptoms was investigated.


METHODS
Mice were sensitized orally to whey, while being fed with a diet containing scGOS/lcFOS and Bifidobacterium breve M-16V (GF/Bb) or a control diet. Galectin-9 expression was determined by immunohistochemistry in the intestine and measured in the serum by ELISA. T-cell differentiation was investigated in the mesenteric lymph nodes (MLN) as well as in galectin-9-exposed peripheral blood mononuclear cells (PBMC) cultures. Sera of the mice were evaluated for the capacity to suppress mast cell degranulation using a RBL-2H3 degranulation assay. In addition, in a double-blind, placebo-controlled multicenter trial, galectin-9 levels were measured in the sera of 90 infants with atopic dermatitis who received hydrolyzed formulae with or without GF/Bb.


RESULTS
Galectin-9 expression by intestinal epithelial cells and serum galectin-9 levels were increased in mice and humans following dietary intervention with GF/Bb and correlated with reduced acute allergic skin reaction and mast cell degranulation. In addition, GF/Bb enhanced T(h)1- and T(reg)-cell differentiation in MLN and in PBMC cultures exposed to galectin-9.


CONCLUSIONS
Dietary supplementation with GF/Bb enhances serum galectin-9 levels, which associates with the prevention of allergic symptoms.
Division of Pharmacology, Utrecht Institute Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands. s.dekivit@uu.nl
S
S
de Kivit
E
E
Saeland
A D
AD
Kraneveld
H J G
HJ
van de Kant
B
B
Schouten
B C A M
BC
van Esch
J
J
Knol
A B
AB
Sprikkelman
L B
LB
van der Aa
L M J
LM
Knippels
J
J
Garssen
Y
Y
van Kooyk
L E M
LE
Willemsen
D000818:Animals; D001644:Bifidobacterium; D015550:Cell Degranulation; D002454:Cell Differentiation; D003876:Dermatitis, Atopic / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D019587:Dietary Supplements; D004311:Double-Blind Method; D004847:Epithelial Cells / Q000378:metabolism; D037161:Galectins / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D041943:Infant Formula / Q000008:administration & dosage* / Q000737:chemistry; D007422:Intestines / Q000166:cytology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D009844:Oligosaccharides / Q000008:administration & dosage* / Q000737:chemistry; D056692:Prebiotics; D019936:Probiotics / Q000008:administration & dosage*; D058616:Synbiotics; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D037161:Galectins; D009844:Oligosaccharides; D056692:Prebiotics