Mice co-administrated with partially hydrolysed whey proteins and prebiotic fibre mixtures show allergen-specific tolerance and a modulated gut microbiota

Abstract

Non-breastfed infants at-risk of allergy are recommended to use a hydrolysed formula before the age of 6 months. The addition of prebiotics to this formula may reduce the allergy development in these infants, but clinical evidence is still inconclusive. This study evaluates (1) whether the exposure duration to different prebiotics alongside a partially hydrolysed whey protein (pHP) influences its’ effectiveness to prevent allergy development and (2) whether the gut microbiota plays a role in this process. Mice orally sensitised with whey and/or cholera toxin were orally treated for six days before sensitization with phosphate buffered saline, whey or pHP to potentially induce tolerance. Two groups received an oligosaccharide diet only from day -7 until -2 (GFshort and GFAshort) whereas two other groups received their diets from day -15 until 37 (GFlong and GFAlong). On day 35, mice underwent an intradermal whey challenge, and the acute allergic skin response, shock score, and body temperatures were measured. At day 37, mice received whey orally and serum mouse mast cell protease-1, SLPI and whey-specific antibodies were assessed. Faecal samples were taken at day -15, -8 and 34. Feeding mice pHP alone during tolerance induction did not reduce ear swelling. The tolerance inducing mechanisms seem to vary according to the oligosaccharide-composition. GFshort, GFlong, and GFAlong reduced the allergic skin response, whereas GFAshort was not potent enough. However, in the treatment groups, the dominant Lactobacillus species decreased, being replaced by Bacteroidales family S24-7 members. In addition, the relative abundance of Prevotella was significantly higher in the GFlong, GFAshort and GFAlong groups. Co-administration of oligosaccharides and pHP can induce immunological tolerance in mice, although tolerance induction was strongest in the animals that were fed oligosaccharides during the entire protocol. Some microbial changes coincided with tolerance induction, however, a specific mechanism could not be determined based on these data.

Three Candidate Probiotic Strains Impact Gut Microbiota and Induce Anergy in Mice with Cow's Milk Allergy

“…A decrease in Prevotella spp. has been reported in allergic infants and children (27), and an increase in this bacterial group was associated with the protective effect of prebiotic treatment in a CMA mouse model (28). Moreover, Prevotella intermedia has been demonstrated to have immunosuppressive effects on in vitro human lymphocyte activation, inhibiting the release of cytokines and expression of the interleukin 2 receptor and CD69 on T cells (29), a mechanism of action in accordance with our observations.…”

Immunonutrition for Pediatric Patients With Cow's Milk Allergy: How Early Interventions Could Impact Long-Term Outcomes

“…The elicited positive effect is completed by the increase of the median concentration of SCFAs, especially butyric acid, as shown by GM metabolomic analysis ( 59 ). Recently, it has been demonstrated that the co-administration of HMOs with partially hydrolyzed whey protein, can induce immunological tolerance in sensitized mice with whey and/or cholera toxin ( 60 ). In an experimental animal study, administration of a prebiotic mixture reduced the allergic skin response, whey-IgG levels, and increased the number of Foxp3 + cells in the proximal small intestine of whey- compared to sham-sensitized mice.…”

Cow’s Milk Allergy: Immunomodulation by Dietary Intervention

“…Adding pectin-derived acidic oligosaccharides to this mixture enhanced Tbet (Th1), IL-10, and TGF-β mRNA expression, which was maintained in the distal small intestine and/or colon [127]. Interestingly, a more recent study [128] showed that co-administration of oligosaccharides and partially hydrolyzed whey protein can induce immunological tolerance in mice orally sensitized with whey and/or cholera toxin on day 35, particularly if the intake was on a daily basis. The oligosaccharide composition seems to influence the tolerance inducing mechanisms and was associated with the decrease of Lactobacillus species, being replaced by Bacteroidales family S24-7 members and with the relative abundance of Prevotella [128].…”

“…At present, despite some promising results mainly related to the effect of specific prebiotics on the gut microbiota, clinical evidence of the beneficial effect of prebiotics in CMA is still inconclusive [128].…”