Increasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundant Bacteroidetes, Proteobacteria, and Actinobacteria phyla were significantly reduced, while the Firmicutes phylum was highly enriched in the FA group (P < 0.05). Abundant Clostridiaceae 1 organisms were prevalent in infants with FA at the family level (P ‫؍‬ 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the genera Enterococcus and Staphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P < 0.05). Infants with IgE-mediated FA had increased levels of Clostridium sensu stricto and Anaerobacter and decreased levels of Bacteroides and Clostridium XVIII (P < 0.05). A positive correlation was observed between Clostridium sensu stricto and serum-specific IgE (R ‫؍‬ 0.655, P < 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.

Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM).Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year.Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048).Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.

Objectives: In this study, we hypothesized that replacing conventional milk, which contains A1 and A2 β-casein proteins, with milk that contains only A2 β-casein in the diet of dairy or milk-intolerant preschoolers (age 5 to 6 years) would result in reduced gastrointestinal symptoms associated with milk intolerance, and that this would correspond with cognitive improvements. Methods: This randomized, double-blind, crossover study aimed to compare the effects of 5 days’ consumption of conventional milk versus milk containing only A2 β-casein on gastrointestinal symptoms, as assessed via visual analog scales, average stool frequency and consistency, and serum inflammatory and immune biomarkers in healthy preschoolers with mild-to-moderate milk intolerance. The study also aimed to compare changes in the cognitive behavior of preschoolers, based on Subtle Cognitive Impairment Test scores. Results: Subjects who consumed milk containing only A2 β-casein had significantly less severe gastrointestinal symptoms as measured by visual analog scales, reduced stool frequency, and improvements in stool consistency, compared with subjects consuming conventional milk. There were significant increases from baseline in serum interleukin-4, immunoglobulins G, E, and G1, and beta-casomorphin-7 coupled to lower glutathione levels, in subjects consuming conventional milk compared with milk containing only A2 β-casein. Subtle Cognitive Impairment Test analysis showed significant improvements in test accuracy after consumption of milk containing only A2 β-casein. There were no severe adverse events related to consumption of either milk product. Conclusions: Replacing conventional milk with milk containing only A2 β-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.

ScopeMilk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study is to determine whether supplementing MFGM in infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies.Methods and ResultsThe serum metabolome and fecal microbiota are analyzed using 1H NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM‐enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula‐fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation did not induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota‐associated metabolites.ConclusionSupplementing MFGM in a formula reduced some metabolic gaps between formula‐fed and breastfed infants.

Regulating the composition of human breastmilk has the potential to prevent allergic diseases early in life. The composition of breastmilk is complex, comprising varying levels of oligosaccharides, immunoactive molecules, vitamins, metabolites, and microbes. Although several studies have examined the relationship between different components of breastmilk and infant food allergies, few have investigated the relationship between microorganisms in breastmilk and infant food allergy. In the present study, we selected 135 healthy pregnant women and their full-term newborns from a cohort of 202 mother–infant pairs. Among them, 69 infants were exclusively breastfed until 6 mo after birth. At follow-up, 11 of the 69 infants developed a food allergy in infancy while 22 showed no signs of allergy. Thirty-three breastmilk samples were collected within 1 mo after delivery, and 123 infant fecal samples were collected at five time points following their birth. These samples were analyzed using microbial 16S rRNA gene sequencing. The abundance and evenness of the milk microbiota and the number of differential bacteria were higher in the breastmilk samples from the non-allergy group than in those from the food allergy group. The non-allergy group showed relatively high abundance of Bifidobacterium, Akkermansia, Clostridium IV, Clostridium XIVa, Veillonella, and butyrate-producing bacteria such as Fusobacterium, Lachnospiraceae incertae sedis, Roseburia, and Ruminococcus. In contrast, the abundance of Proteobacteria, Acinetobacter, and Pseudomonas in breastmilk was higher in the food allergy group. A comparison of the changes in dominant differential breastmilk microbiota in the intestinal flora of the two groups of infants over time revealed that the changes in Bifidobacterium abundance were consistent with those in the breastmilk flora. Functional pathway prediction of breastmilk microflora showed that the enhancement of the metabolic pathways of tyrosine, tryptophan, and fatty acids was significantly different between the groups. We suggest that changes in the breastmilk microbiota can influence the development of food allergies. Breastmilk contains several microbes that have protective effects against food allergies, both by influencing the colonization of intestinal microbiota and by producing butyrate. This study may provide new ideas for improving infant health through early intervention with probiotics.

The gut microbiota plays a crucial role in food allergies. We sought to identify characteristics of the maternal gut microbiota in the third trimester and the infant gut microbiota in early life and the association of these microbiotas with infant food allergy. A total of 68 healthy pregnant women and their full-term newborns were selected from a cohort of 202 mother–infant pairs; among them, 24 infants had been diagnosed with food allergy within 1 year of age, whereas 44 infants were healthy without allergic symptoms. We collected 65 maternal fecal samples before delivery and 253 infant fecal samples at five time points following birth. Fecal samples were microbiologically analyzed using 16S rRNA gene sequencing. Holdemania abundance in the maternal gut microbiota in the third trimester was significantly higher in the non-allergy group than in the food allergy group (P = 0.036). In the infant gut microbiota, Holdemania was only found in meconium samples; its abundance did not differ significantly between the two groups. The change in the abundance of Actinobacteria over time differed between the non-allergy and food allergy groups (FA, P = 0.013; NA, P = 9.8 × 10−5), and the change in the abundance of Firmicutes over time differed significantly in the non-allergy group (P = 0.023). The abundances of genera Anaerotruncus, Roseburia, Ruminococcus, and Erysipelotricaceae were significantly different between the non-allergy and food allergy groups at different time points. Our results showed that maternal carriage of Holdemania during the third trimester strongly predicted the absence of food allergies in infants; there was no correlation between the presence of food allergies and the abundance of Holdemania in the infant gut microbiota. More dynamic fluctuations in phyla Actinobacteria and Firmicutes early in life protect against food allergy. Thus, the enrichment of the infant gut microbiota early in life with short-chain fatty acid-producing bacteria may be beneficial in preventing the development of food allergies in infants.

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The early-life microbiota triggers life-long effects on physiological functions and health disorders. Previous studies in adult twins or animal models have revealed associations between host genetics and the harmonious microbiota. However, such associations may be obscured by the fact that each intra-pair of twins will continually encounter various environmental factors as they grow up. Here, we collected the meconium samples from nineteen dizygotic pairs (DZ, n = 38) and nine monozygotic pairs (MZ, n = 18) with cesarean delivery, and 16S rRNA gene sequencing was performed to profile the microbiome at birth. Diversity analysis showed that alpha diversity was not significantly different between two groups, whereas beta diversity of MZ twins was significantly lower than that of either DZ twins or unrelated individuals (i.e., randomly selected individual pairs of non-twinship) (p < 0.05). Two groups had very similar microbial classifications but different relative abundances of certain taxa including more Firmicutes (p = 0.05, Wilcoxon test) at the phylum level and lower abundances of five genera (p < 0.05) in DZ group compared to MZ group, including Rheinheimera, Proteus, SMB53, Sphingobium, and Megamonas. Co-occurrence analysis in each group showed slightly more complicated microbial interactions in DZ than MZ twins, although 22 shared bacterial genera co-existed in two groups, with both Rheinheimera and Megamonas having different centralities in their respective co-occurrence networks. Mean intra-class correlation coefficient (ICC) were also significantly higher for MZ (0.312) compared to DZ twins (0.138) (p < 0.05).The predicted microbial gene functions related to carbohydrate were higher in DZ group, whereas folding, sorting, degradation, cell motility pathways and energy metabolism were markedly over-represented in the microbiota of MZ group. In summary, our study uncovered that microbial diversity and components of the meconium microbiome between DZ and MZ twins were partially consistent with that in singleton neonates by cesarean delivery, but several distinctions related to the heritability supported genetic contributions to intestinal microbiome in early life.