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

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.