Increasing evidence suggests that perturbations in the intestinal microbiota in early infancy are implicated in the pathogenesis of food allergy (FA); existing evidence on the structure and composition of the intestinal microbiota in human beings with FA is limited and conflicting. The main object of the study was to compare the faecal microbiota between healthy and cow's milk allergy (CMA) infants at the baseline immediately after the diagnosis, and to evaluate the changes in the faecal microbiota after 6 months of treatment of CMA infants with hypoallergenic formula (HF), compared with healthy children fed on standard milk formulae. Sixty infants younger than 4 months of age with challenge-proven CMA and 60 healthy age-matched children were investigated in this prospective case - control follow-up study. Faecal samples were collected at baseline and at 6 months of follow-up, microbial diversity and composition were characterized by high-throughput 16S rRNA sequencing. The average age (±SD) of the infants at inclusion was 2.9 ± 1.0 months. Children with CMA have lower gut microbiota diversity and an elevated Enterobacteriaceae to Bacteroidaceae (E/B ratio) in early infancy compared with healthy children (115.8 vs. 0.8, P = 0.0002). After 6 months of treatment with HF, CMA infants had a higher Lactobacillaceae (6.3% vs. 0.5%, P = 0.04) and lower Bifidobacteriaceae (0.3% vs. 8.2%, P = 0.03) and Ruminococcaceae (1.5% vs. 10.5%, P = 0.03) abundance compared with control children. : Low gut microbiota diversity and an elevated E/B ratio in early infancy may contribute to the development of FA, including CMA. A strict elimination diet may weaken FA by reducing E/B ratio and promoting a gut microbiota that would benefit the acquisition of oral tolerance.

Breastfeeding has been shown to have a protective effect on the occurrence of necrotizing enterocolitis (NEC), but the mechanism remains unclear. In the context of NEC pathogenesis, many of the protective properties of exosomes on the intestinal epithelial compartment make it an ideal therapeutic target. In the present study, our hypothesis was that intestinal stem cells (ISCs) would be protected from injury by human milk-derived exosomes (HMDEs). Human breast milk was collected, and exosomes were isolated using ExoQuick reagent. Magnetic-activated cell sorting isolation of prominin-1+ ISCs was performed from small intestines of neonatal rat. ISCs were treated with or without H2O2, and HMDEs, an equal volume of HMDE-free milk, or a control solution [phosphate-buffered solution (PBS)] was added, respectively. In the absence of HMDEs, exposure of ISCs to H2O2 led to decreased cell viability. However, addition of HMDEs to ISCs exposed to H2O2 led to significantly increased ISC viability. There was a significant upregulation of mRNA expression of Axin2, c-Myc, and Cyclin D1 genes of the Wnt/β-catenin axis in ISCs treated with HMDEs (6.99 ± 2.34, 4.21 ± 1.68, 6.17 ± 2.22, respectively, P < 0.05 for all), as compared to control. In the presence of carnosic acid (a specific Wnt/β-catenin signaling inhibitor), the cell viability was significantly decreased. Thus, HMDEs protect ISCs from oxidative stress injury in vitro, which were possibly mediated via the Wnt/β-catenin signaling pathway. Our findings indicate that oral administration of HMDEs might be a promising measure in treating NEC or in preventing the development of NEC in high-risk infants when breast milk is not available.

Children with CMA who followed an elimination diet could achieve a normal nutritional status, except for relatively lower plasma leptin levels, at the age of 2. Further studies with larger cohorts and research on the long-term consequences of these early differences are needed.

Human milk lipids have important biological effects on recipient infants. The objective of this study is to comprehensively describe lipidomic differences between preterm milk of different gestational ages and term milk over the course of lactation. Colostrum (<5 d postpartum, n = 20 for very preterm [VPT], n = 20 for moderately preterm [MPT] and n = 30 for full-term [FT]) and mature milk (at four weeks postpartum, n = 11 for extremely preterm [EPT], n = 23 for VPT, n = 21 for MPT, and n = 25 for FT) are collected from 88 mothers who had delivered premature babies and 39 who had delivered term infants. It is found that the relative abundance of 10 out of 43 lipid subclasses are persistently higher in preterm milk than in term milk over the course of lactation. Diacylglycerol and fatty acid ester of hydroxyl fatty acid (FAHFA) lipid classes contribute most to the differences. The ten individual lipid species differing most significantly between VPT and FT colostrum are mainly part of the phosphatidylethanolamine and diacylglycerol groups. Levels of lipid species from the FAHFA class are significantly higher in both EPT and VPT mature milk than in their FT counterpart. The lipids in preterm and term milk show substantial differences, which may be critical for postnatal growth. Practical applications: These findings expand the current understanding of lipid components in human milk and provide important laboratory data for the future management of infant feeding, particularly of fragile, high risk EPT and VPT infants.

Background Studies are beginning to emerge on the important biological effects of the milk lipids exerted on the recipient infant, especially on the premature infants. The aim of this study was to comprehensively describe lipidomic differences between preterm milk of different gestational ages with the term milk over the course of lactation. Methods Breast milk samples were collected from 88 mothers giving birth prematurely and 39 mothers delivering at full-term (FT). Lipid profiles were assessed using an LC-MS/MS metabolomics strategy. Orthogonal partial least-squares discriminant analysis (OPLS-DA) and pathway analysis were subsequently performed. Results The OPLS-DA score plots significantly distinguished the lipids in preterm milk of different gestation ages from their counterparts in term milk. The concentrations of 10 out of 43 lipid subclasses were found to be persistently higher in preterm compared to term milk over the course of lactation; the diacylglycerol (DAG) and a bioactive subclass fatty acid ester of hydroxyl fatty acid (FAHFA) contributed the most to the differences. In terms of individual lipid species, the ten highest substances found in very preterm (VPT) colostrum compared to FT colostrum mainly come from the phosphatidylethanolamine class and the DAG species. Lipid species from the free fatty acid and FAHFA classes were significantly higher in either extremely preterm (EPT) or VPT mature milk (variable importance in projection > 1, P < 0.0001 for all). The differential lipids between each preterm group and its term counterpart were predicted to be mainly involved in six metabolic pathways, including glycerophospholipid metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, linoleic acid metabolism, alpha-Linolenic acid metabolism, arachidonic acid metabolism and glycerolipid metabolism. Conclusions The lipids in preterm and term milk showed substantial differences, which may be critical for postnatal growth, as well as the neural and immune development of newborns, especially EPT and VPT.