(P30-014-23) Immunomodulatory Effects of Galacto-oligosaccharides

Objectives: Food allergies in infancy have become a growing public health concern. According to the CDC, food allergies are estimated to impact over 8% of children in the US. Galacto-oligosaccharides (GOS), structurally similar to human milk oligosaccharides, modulate the gut microbiota and have beneficial effects on host health. In an early pilot experiment, GOS feeding resulted in non-statistically significant reductions in peanut-specific IgE, anaphylaxis, intestinal permeability, and increased relative abundance of Akkermansia and Bifidobacterium in peanut-sensitized CC027/GeniUnc mice. We hypothesize that immunomodulation by GOS is mediated through (a) direct interaction between GOS and the carbohydrate recognition domain (CRD) of Galectin-1 (Gal-1), and the subsequent activation of Lgals-1 gene expression, and (b) indirect effects via tryptophan metabolites produced by Bifidobacterium species stimulated by the prebiotic.

Methods: We confirmed differential expression of Lgals-1 in mice fed GOS compared with control diets and human primary colonic cells exposed to prebiotic and metabolite treatments by reverse transcription-quantitative (q) PCR. Computational molecular docking was used to predict the binding affinity between carbohydrate ligands and Gal-1.

Results: Here, we showed in mice and primary human intestinal cells that GOS induced the expression of Lgals-1, which encodes Gal-1, a glycoprotein with immunomodulatory effects and an established role in suppressing allergic asthma.

In the mice study, GOS significantly increased Lgals-1 expression in the colon of young but not old mice. Computational predictions confirmed the binding affinity between GOS and Gal-1, suggesting a direct interaction. We also showed that GOS interacted directly with human primary intestinal cells inducing Lgals-1 expression.

Additionally, we showed that GOS induced Lgals-1 expression in the human intestinal cells by enhancing Bifidobacterium, providing an indirect induction pathway of Lgals-1 by GOS.

Conclusions: Our study lays the groundwork for mechanistic research exploring a potential prebiotic role in modulating the immune system, specifically for preventing or treating food allergies.

Funding Sources: Center for Gastrointestinal Biology and Disease (CGIBD P30 DK034987); UNC Nutrition Obesity Research Center (NORC P30 DK056350)