Partially Hydrolysed Whey Has Superior Allergy Preventive Capacity Compared to Intact Whey Regardless of Amoxicillin Administration in Brown Norway Rats

Abstract

BackgroundIt remains largely unknown how physicochemical properties of hydrolysed infant formulas influence their allergy preventive capacity, and results from clinical and animal studies comparing the preventive capacity of hydrolysed infant formula with conventional infant formula are inconclusive. Thus, the use of hydrolysed infant formula for allergy prevention in atopy-prone infants is highly debated. Furthermore, knowledge on how gut microbiota influences allergy prevention remains scarce.ObjectiveTo gain knowledge on (1) how physicochemical properties of hydrolysed whey products influence the allergy preventive capacity, (2) whether host microbiota disturbance influences allergy prevention, and (3) to what extent hydrolysed whey products influence gut microbiota composition.MethodsThe preventive capacity of four different ad libitum administered whey products was investigated in Brown Norway rats with either a conventional or an amoxicillin-disturbed gut microbiota. The preventive capacity of products was evaluated as the capacity to reduce whey-specific sensitisation and allergic reactions to intact whey after intraperitoneal post-immunisations with intact whey. Additionally, the direct effect of the whey products on the growth of gut bacteria derived from healthy human infant donors was evaluated by in vitro incubation.ResultsTwo partially hydrolysed whey products with different physicochemical characteristics were found to be superior in preventing whey-specific sensitisation compared to intact and extensively hydrolysed whey products. Daily oral amoxicillin administration, initiated one week prior to intervention with whey products, disturbed the gut microbiota but did not impair the prevention of whey-specific sensitisation. The in vitro incubation of infant faecal samples with whey products indicated that partially hydrolysed whey products might confer a selective advantage to enterococci.ConclusionsOur results support the use of partially hydrolysed whey products for prevention of cow’s milk allergy in atopy-predisposed infants regardless of their microbiota status. However, possible direct effects of partially hydrolysed whey products on gut microbiota composition warrants further investigation.

Amoxicillin does not affect the development of cow’s milk allergy in a Brown Norway rat model

“…We previously reported that amoxicillin promotes classical FoxP3 + CD25 + Treg cells in the SI, but not in the blood, mLN or PP after a short 1‐week regimen of daily administrations in BN rats 28 . However, this effect seems only to be transient, as amoxicillin did not affect the overall frequency of classical FoxP3 + CD25 + Tregs in the intestine five weeks after a 4‐week regimen of daily administrations in BN rats 25 . Combined, the findings indicate that amoxicillin has limited long‐term effects on homeostatic immune regulation and risk for food allergy development in the gut.…”

“…The main adverse reaction to amoxicillin treatment is diarrhoea, 22 which likely can be attributed to the disturbance of the gut microbiota composition in humans 23,24 . We previously found that amoxicillin did not affect the development of oral tolerance to cow's milk whey protein concentrate (WPC) in a Brown Norway (BN) rat model of CMA 25 . This finding indicates that this particular antibiotic does not promote food allergy by inhibiting homeostatic tolerance induction in the gut.…”

Alternatives to Cow’s Milk-Based Infant Formulas in the Prevention and Management of Cow’s Milk Allergy

“…Results from animal studies are in line with the results from human studies, with some studies showing a preventive effect of pHFs on CMA development, while other studies did not show such effect. For example, studies by Graversen et al, Jensen et al, and Fritsche et al showed that partially hydrolysed whey had a capacity to induce oral tolerance to intact whey proteins [ 151 , 162 , 163 ]. Further, Chikhi et al showed that partially hydrolysed whey induced a partial prevention of sensitisation to β-lactoglobulin but no prevention of sensitisation to caseins [ 164 ].…”

“…For example, lack of the preventive effect of partially hydrolysed whey on casein sensitisation development may be explained by the lack of casein derived peptides in this type of product and, as a consequence, lack of the oral tolerance induction towards caseins as explained in the study by Chikhi et al [ 164 ]. In addition, different pHFs characteristics may be explained by the huge variation in DH, as illustrated by Graversen et al [ 162 ].…”

Free amino acids in human milk: a potential role in early life growth and immunity

“…A role for glutamine in the preservation of intestinal health and in the promotion of intestinal growth and barrier function is further supported by the findings of studies in young animals. For instance, in piglets, dietary glutamine supplementation protected against E.coli-and endotoxin-induced intestinal damage [114,119,120]. Moreover, dietary Whether dietary glutamine can also prevent bacterial translocation in neonatal animals, however, remains to be examined.…”