Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis

ObjectiveAnalyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers.Patients and MethodsFourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry.ResultsThe fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients.ConclusionsThe differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins. image A role of gut microbiota in cow's milk protein allergy (CMPA) has been described, but no reports exist comparing IgE mediated and non-IgE mediated (NIM) cases. Current protocols for NIM forms of CMA diagnosis are based on the response to a clinical elimination diet and reappearance of symptoms after an oral challenge. The search for novel biomarkers in NIM forms of CMA, such as allergic proctocolitis, has been elusive.What is New Differences in bifidobacteria composition were revealed between IgE and non-IgE infants diagnosed with CMPA. Lack of the species B. longum and Bifidobacterium breve characterized the intestine of patients with nNIM forms. Fecal immune mediators, in particular, IL-1ra and platelet derived growth factor-BB, could be useful in the diagnosis of NIM CMPA.