Novel Mechanisms Underlying the Therapeutic Effect of Glycomacropeptide on Allergy: Change in Gut Microbiota, Upregulation of TGF-β, and Inhibition of Mast Cells

Abstract

Background: The prevalence of allergic diseases is globally increasing. We have previously described that glycomacropeptide (GMP), a bioactive milk peptide, has therapeutic value in experimental models of skin hypersensitivity, anaphylaxis, and asthma, as it prevents an excessive T helper type 2 cell immune response. The aim of this study was to analyze the effect of GMP on key elements directly involved in the development or control of allergy, in order to improve the precise knowledge about its mechanism of action. Methods: Rats were systemically sensitized with ovalbumin and orally treated with GMP. Levels of Lactobacillus, Bifidobacterium, and Bacteroides were analyzed in their feces. Splenocytes were isolated and the production of transforming growth factor (TGF)-β by allergens was measured. Intradermal skin reactions were developed to evaluate in vivo activation of mast cells. Peritoneal mast cells were isolated and activated by the allergen, and histamine secretion was determined. Results: GMP administration increased the amount of intestinal Lactobacillus and Bifidobacterium of allergen-sensitized animals after 3 days of treatment. The increase in Bacteroides was also significant, but only after 17 days of GMP administration. Ten days after treatment cessation, Lactobacillus and Bacteroides were still elevated. GMP intake also elevated the production of TGF-β in the splenocytes of sensitized animals. In addition, treatment with GMP attenuated mast cell activation by the allergen and inhibited histamine secretion, without affecting the number of mast cells. Conclusions: The prebiotic action of GMP on allergy-protective microbiota, an increase in TGF-β production, and a reduction in mast cell response to allergens are novel mechanisms that explain the antiallergic activity of GMP.

Retention of Microbiota Diversity by Lactose-Free Milk in a Mouse Model of Elderly Gut Microbiota

“…Increase in Bacteroides population due to GMP-supplementation has been reported in mouse model studies 27,28 . Milk and subsequently GMP contain highly sialylated carbohydrate components 10 .…”

“…Sawin et al 28 reported that a GMP-supplemented diet significantly decreased the caecal and colonic relative abundance of Desulfovibrio and Proteobacteria in wild type and PKU mice. Interestingly, GMP selectivity for promoting growth of Bacteroidetes taxa has also been reported 27,28 .…”

Glycomacropeptide: Biological Activities and Uses

“…In recent years, a Mexican laboratory led by Salinas [55,[59][60][61] has focused on the study of the immunomodulatory activity of GMP in experimental allergy models. They found that oral administration of GMP to rats before and during sensitization with allergen significantly reduces the level of allergen-specific IgE in serum, and also decreases the proliferative response and the production of IL-13 by splenocytes stimulated by the allergen [55].…”

Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches

“…Animal models also indicate that Casein GMP could mediate intestinal inflammation via the gut microbiota [107–109], with administration associated with reductions in Proteobacteria, genera Desulfovibrio (from 30-35% to 7%), and increases in acetate, propionate and butyrate levels (cecum) [110]. Recent data proposed that GMP exerts anti-allergenic activity via modulation of gut microbiota [111]. Specifically, the GMP-induced increase in Lactobacillus , Bifidobacterium and Bacteroides , attributed to increased TGG-B production and reductions in mast cells [111].…”

“…Recent data proposed that GMP exerts anti-allergenic activity via modulation of gut microbiota [111]. Specifically, the GMP-induced increase in Lactobacillus , Bifidobacterium and Bacteroides , attributed to increased TGG-B production and reductions in mast cells [111]. Clinical trials for active distal colitis in UC patients have reported casein GMP is well-tolerated, exerting similar disease-modifying effects to that of mesalazine [112, 113].…”