Abstract
Prebiotic galacto-oligosaccharides (GOS) were shown to support mucosal immune development by enhancing regulatory-type Th1 immune polarization induced by synthetic CpG oligodeoxynucleotides (TLR9 agonist mimicking a bacterial DNA trigger). Epithelial-derived galectin-9 was associated with these immunomodulatory effects. We aimed to identify the most active fractions within GOS based on the degree of polymerization (DP), and to study the immunomodulatory capacities of DP3-sized β-3′galactosyllactose (β-3′GL) using a transwell co-culture model of human intestinal epithelial cells (IEC) and activated peripheral blood mononuclear cells (PBMC). IEC were apically exposed to different DP fractions of GOS or β-3′GL in the presence of CpG, and basolaterally co-cultured with αCD3/CD28-activated PBMC, washed, and incubated in fresh medium for IEC-derived galectin analysis. Only DP3-5 in the presence of CpG enhanced galectin-9 secretion. DP3-sized β-3′GL promoted a regulatory-type Th1 response by increasing IFNγ and IL-10 or galectin-9 concentrations as compared to CpG alone. In addition, IEC-derived galectin-3, -4, and -9 secretion was increased by β-3′GL when combined with CpG. Therefore, the GOS DP3-5 and most effectively DP3-sized β-3′GL supported the immunomodulatory properties induced by CpG by enhancing epithelial-derived galectin secretion, which, in turn, could support mucosal immunity.
Highlights
Non-digestible oligosaccharides (NDO) are the third major component in human milk [1]
Various clinical studies have shown that this GOS/FOS mixture promoted the growth of commensal bacteria, induced stool softening, reduced the incidence of infections and the incidence of atopic dermatitis, as well as modulated the antibody profile in infants at high risk of allergy [3–8]
The immunomodulatory effects of degree of polymerization (DP) fractions isolated from GOS were studied using a transwell intestinal epithelial cells (IEC)/peripheral blood mononuclear cells (PBMC) co-culture model used to investigate the crosstalk between epithelial cells and innate, as well as adaptive, immune cells
Summary
Non-digestible oligosaccharides (NDO) are the third major component in human milk [1]. Based on the amount and structure diversity of NDO in human milk, a 9:1 mixture of short-chain galacto- and long-chain fructo-oligosaccharides (GOS/FOS) was studied for its effects on the microbiota and the intestinal mucosa [2]. Various clinical studies have shown that this GOS/FOS mixture promoted the growth of commensal bacteria, induced stool softening, reduced the incidence of infections and the incidence of atopic dermatitis, as well as modulated the antibody profile in infants at high risk of allergy [3–8]. Biomolecules 2022, 12, 384 with atopic dermatitis, this synbiotic mixture was found to enhance serum galectin-9 levels after 12 weeks of intervention, in association with reduced atopic dermatitis symptom scores and lower risks of developing asthma [10,13,14]. GOS supported the absorption of minerals such as iron and calcium in young infants [21,22], as well as lowered the incidence and severity of travelers’ diarrhea in humans travelling to high-risk countries [23]
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