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

Analyze 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. Fourteen 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. The 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. The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Castro AM ，Gutiérrez-Díaz I ，Saiz ML ，Navarro S ，Suárez M ，Carbajal I ，García Á ，Sariego L ，Toyos P ，Rodríguez S ，Jiménez S ，González D ，Molinos C ，Pérez D ，Fernández P ，Suárez-Alvarez B ，Margolles A ，Díaz JJ ，Delgado S ... -  《-》

Microbiota and Derived Parameters in Fecal Samples of Infants with Non-IgE Cow's Milk Protein Allergy under a Restricted Diet.

Díaz M ，Guadamuro L ，Espinosa-Martos I ，Mancabelli L ，Jiménez S ，Molinos-Norniella C ，Pérez-Solis D ，Milani C ，Rodríguez JM ，Ventura M ，Bousoño C ，Gueimonde M ，Margolles A ，Díaz JJ ，Delgado S ... -  《Nutrients》

Fecal Changes Following Introduction of Milk in Infants With Outgrowing Non-IgE Cow's Milk Protein Allergy Are Influenced by Previous Consumption of the Probiotic LGG.

Guadamuro L ，Diaz M ，Jiménez S ，Molinos-Norniella C ，Pérez-Solis D ，Rodríguez JM ，Bousoño C ，Gueimonde M ，Margolles A ，Delgado S ，Díaz JJ ... -  《Frontiers in Immunology》

Influences of non-IgE-mediated cow's milk protein allergy-associated gut microbial dysbiosis on regulatory T cell-mediated intestinal immune tolerance and homeostasis.

Gut microbial dysbiosis is closely associated with cow's milk protein allergy (CMPA) during infancy. Recent research has highlighted the crucial role of the commensal microbiota-induced intestinal regulatory T (Treg) cell response in the development of oral tolerance and protection against IgE-mediated food allergies. However, the influences of CMPA (particularly non-IgE-mediated CMPA)-associated microbial dysbiosis on Treg cell-mediated intestinal immune tolerance and homeostasis remain poorly characterized. To investigate this issue, fecal microbiota from infant donors with food protein-induced allergic proctocolitis (FPIAP) associated with cow's milk, which is the most frequent clinical type of non-IgE-mediated gastrointestinal CMPA, and from age-matched healthy controls were transplanted into germ-free mice in this study. Two weeks post fecal microbiota transplantation, the gut microbiome of the recipient mice was analyzed by 16S rRNA gene sequencing, and the intestinal immunological alterations associated with the Treg cell compartment and intestinal immune homeostasis were detected. The specific gut microbial phylotypes that were potentially responsible for the disruption of intestinal immune homeostasis were also analyzed. We observed that the main characteristics of the gut microbiome in infant donors could be stably maintained in recipient mice. We also found that mice colonized with the gut microbiome from infants with cow's milk-induced FPIAP showed significant deficiencies in the accumulation and function of intestinal Treg cells. Furthermore, these mice showed disrupted intestinal immune homeostasis, which was characterized by an overactivated Th2 biased immune response. We further identified two potentially pathogenic genera that contribute to this disruption. Overall, our results highlight a destructive effect of non-IgE-mediated CMPA-associated microbial dysbiosis on intestinal immune tolerance and homeostasis. We believe these findings will help improve our understanding of the gut microbiota-mediated pathogenesis of non-IgE-mediated CMPA in the future.

Wang J ，Zheng S ，Yang X ，Huazeng B ，Cheng Q ... -  《-》

[Specific changes in gut microbiota and short-chain fatty acid levels in infants with cow's milk protein allergy].

Yu ZD ，Yue LL ，Wang ZH ，Wang RZ ，Li LF ，Zhang WC ，Li XQ ... -  《-》