Feeding formula, intestinal microbiota and tolerance acquisition in children with non-IgE mediated cow`s milk allergy

Trabajo presentado en el 51st Annual Meeting European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), celebrado en Ginebra (Suiza) del 9 al 12 de mayo de 2018[Objectives and study] Cow`s milk protein allergy (CMPA) is the most common food allergy in the first year of life. A great proportion of children acquire tolerance before the age of 3 years , when a stable adult-like gut microbiota is being established. Associations between CMPA in infants and altered intestinal microbiota structure have been previously pointed out. However, non-IgE mediated forms remains poorly understood and are less studied than IgE mediated ones. Current guidelines recommend the use of extensively hydrolyzed formula (EHF) for CMPA as first choice, but other formulas based on vegetable proteins are also employed in daily practice. The aim of our study was to give clues on the role of type of feeding, microbiota composition and sensitization in non-IgE CMPA children. [Methods] Eighteen infants between 1 and 2 years old, diagnosed with non-IgE CMPA (clear positive oral challenge and a negative skin prick test) were recruited at different regional hospitals in Northern Spain (Asturias). They all were on exclusion diet and provided stool samples for the study. A detailed medical history, including type of feeding and formula used were recorded by the clinicians. After six months of milk exclusion a standardized oral challenge was performed under medical supervision. A control group of 10 age-matched healthy infants with normal diet consuming milk proteins were included in the study. Fecal samples of both groups were analyzed by high-throughput DNA sequencing of 16S rRNA gene amplicons (Illumina technology). [Results] Five of the eighteen CMPA infants were fed vegetable protein-based formulas. Of these, three were fed rice formula and, interestingly, none of them developed tolerance. These three children presented a clear distinct microbiota colonization pattern, characterized by a low abundancy of Bifidobacteria (less than 0.25% of assigned reads) and clustered separated from those CMPA infants who were consuming EHF and were tolerant to cow¿s milk after the challenge. Differences in the composition of the gut microbial communities between CMPA and healthy children were also observed. Non-allergic infants under unrestricted diet showed a significantly higher proportion of Bacteroides (p=0,001) as compared to CMPA infants. [Conclusion] Formula and type of feeding can determinate gut microbiota colonization and influence food allergy resolution and tolerance acquisition in non-IgE CMPA cases during the first two years of life.Peer reviewe