Early-life gut microbiome and egg allergy.

Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10-4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis Padj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10-4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention.

Fazlollahi M ，Chun Y ，Grishin A ，Wood RA ，Burks AW ，Dawson P ，Jones SM ，Leung DYM ，Sampson HA ，Sicherer SH ，Bunyavanich S ... -  《-》

Early-life gut microbiome composition and milk allergy resolution.

Gut microbiota may play a role in the natural history of cow's milk allergy. We sought to examine the association between early-life gut microbiota and the resolution of cow's milk allergy. We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43; ANOVA P = .034). Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy.

Bunyavanich S ，Shen N ，Grishin A ，Wood R ，Burks W ，Dawson P ，Jones SM ，Leung DYM ，Sampson H ，Sicherer S ，Clemente JC ... -  《-》

The age-specific microbiome of children with milk, egg, and peanut allergy.

Immune regulation by gut microbiota is affected by dysbiosis and may precede food allergy onset. Prior studies lacked comparisons stratified by age and clinical phenotype. To assess the microbiome of children with food allergy (<3 years, 3-18 years) compared with similar aged children without food allergy. A real-world prospective cross-sectional study performed from 2014 to 2019 recruited children highly likely to have milk, egg, or peanut allergy defined by history and serum IgE or confirmed by food challenge. 16S ribosomal RNA sequencing identified stool microbial DNA. Alpha and beta diversity was compared between groups with food allergy and healthy controls stratified by age. Differential abundance for non a priori taxa was accepted at absolute fold-change greater than 2 and q value less than 0.05. A total of 70 patients were included (56 with food allergy and 14 healthy controls). Groups were not significantly different in age, gender at birth, race, mode of delivery, breastfeeding duration, or antibiotic exposure. Younger children with food allergy had similar alpha diversity compared with controls. Beta diversity was significantly different by age (P = .001). There was differential abundance of several a priori (P < .05) taxa (including Clostridia) only in younger children. Both a priori (including Coprococcus and Clostridia) and non a priori (q < 0.05) Acidobacteria_Gp15, Aestuariispira, Tindallia, and Desulfitispora were significant in older children with food allergy, especially with peanut allergy. Dysbiosis associates with food allergy, most prominent in older children with peanut allergy. Younger children with and without food allergy have fewer differences in gut microbiota. This correlates with clinical observations of persistence of peanut allergy and improved efficacy and safety of oral immunotherapy in younger children. Age younger than 3 years should be considered when initiating therapeutic interventions.

Ponda P ，Cerise JE ，Navetta-Modrov B ，Kiehm J ，Covelli GM ，Weiss J ，Lee AT ... -  《-》

A prospective microbiome-wide association study of food sensitization and food allergy in early childhood.

Alterations in the intestinal microbiome are prospectively associated with the development of asthma; less is known regarding the role of microbiome alterations in food allergy development. Intestinal microbiome samples were collected at age 3-6 months in children participating in the follow-up phase of an interventional trial of high-dose vitamin D given during pregnancy. At age 3, sensitization to foods (milk, egg, peanut, soy, wheat, walnut) was assessed. Food allergy was defined as caretaker report of healthcare provider-diagnosed allergy to the above foods prior to age 3 with evidence of IgE sensitization. Analysis was performed using Phyloseq and DESeq2; P-values were adjusted for multiple comparisons. Complete data were available for 225 children; there were 87 cases of food sensitization and 14 cases of food allergy. Microbial diversity measures did not differ between food sensitization and food allergy cases and controls. The genera Haemophilus (log2 fold change -2.15, P=.003), Dialister (log2 fold change -2.22, P=.009), Dorea (log2 fold change -1.65, P=.02), and Clostridium (log2 fold change -1.47, P=.002) were underrepresented among subjects with food sensitization. The genera Citrobacter (log2 fold change -3.41, P=.03), Oscillospira (log2 fold change -2.80, P=.03), Lactococcus (log2 fold change -3.19, P=.05), and Dorea (log2 fold change -3.00, P=.05) were underrepresented among subjects with food allergy. The temporal association between bacterial colonization and food sensitization and allergy suggests that the microbiome may have a causal role in the development of food allergy. Our findings have therapeutic implications for the prevention and treatment of food allergy.

Savage JH ，Lee-Sarwar KA ，Sordillo J ，Bunyavanich S ，Zhou Y ，O'Connor G ，Sandel M ，Bacharier LB ，Zeiger R ，Sodergren E ，Weinstock GM ，Gold DR ，Weiss ST ，Litonjua AA ... -  《-》

Allergy associations with the adult fecal microbiota: Analysis of the American Gut Project.

Hua X ，Goedert JJ ，Pu A ，Yu G ，Shi J ... -  《EBioMedicine》