Gut changes with milk introduction in infants with outgrowing non-IgE cow's milk protein allergy

[Objectives and Study] Cow's milk protein allergy (CMPA) is very common in infancy. Elimination diet is currently, the only therapeutic option available. Standardized oral milk challenges (SOC) are performed to determine tolerance development. The aim of our study was to analyze changes in feces of infants with non-IgE mediated CMPA after successful milk challenges (tolerance development) regarding microbiota composition and metabolic and cytokine profile [Methods]: Twelve non-IgE mediated CMPA children consuming extensively hydrolyzed formulas for at least 6 months ( 4 consumed formulas supplemented with Lactobacillus rhamnosus GG (LGG) ). In all cases a SOC was scheduled in order to determine tolerance acquisition. All 12 infants provided three consecutive stool samples: one before performing the SOC, one after a week and one after a month. Gut microbiota was determined through high-throughput sequencing. Microbial derived metabolites were analyzed by chromatographic methods. Fecal cytokines related to Th1/Th2 balance were also determined. [Results] With the re-introduction of milk, lactic-acid bacteria, in particular the genus Lactococcus, increased significantly. The content of some microbial metabolites, such as escatol, increased, meanwhile branched chain fatty acids diminished. After SOC, differences in TNF-a and butyrate levels were observed between infants consuming consume LGG supplemented formulas and those without probiotic supplementation. [Conclusions] These findings indicate that introduction of dairy products is followed by modifications in infant´s gut environment through maturation of the microbiota and its metabolic products. Consumption of probiotics may tune these profiles.