Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting.

Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment. We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting. We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography. As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze. Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.

Arrieta MC ，Arévalo A ，Stiemsma L ，Dimitriu P ，Chico ME ，Loor S ，Vaca M ，Boutin RCT ，Morien E ，Jin M ，Turvey SE ，Walter J ，Parfrey LW ，Cooper PJ ，Finlay B ... -  《-》

Composition and Associations of the Infant Gut Fungal Microbiota with Environmental Factors and Childhood Allergic Outcomes.

Boutin RCT ，Sbihi H ，McLaughlin RJ ，Hahn AS ，Konwar KM ，Loo RS ，Dai D ，Petersen C ，Brinkman FSL ，Winsor GL ，Sears MR ，Moraes TJ ，Becker AB ，Azad MB ，Mandhane PJ ，Subbarao P ，Turvey SE ，Finlay BB ... -  《mBio》

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 ... -  《-》

Having older siblings is associated with gut microbiota development during early childhood.

Laursen MF ，Zachariassen G ，Bahl MI ，Bergström A ，Høst A ，Michaelsen KF ，Licht TR ... -  《BMC MICROBIOLOGY》

Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood.

Establishment of the gastrointestinal microbiota during infancy affects immune system development and oral tolerance induction. Perturbations in the microbiome during this period can contribute to development of immune-mediated diseases. We monitored microbiota maturation and associations with subsequent development of allergies in infants and children. We collected 1453 stool samples, at 5, 13, 21, and 31 weeks postpartum (infants), and once at school age (6-11 years), from 440 children (49.3% girls, 24.8% born by cesarean delivery; all children except for 6 were breastfed for varying durations; median 40 weeks; interquartile range, 30-53 weeks). Microbiota were analyzed by amplicon sequencing. Children were followed through 3 years of age for development of atopic dermatitis; data on allergic sensitization and asthma were collected when children were school age. Diversity of fecal microbiota, assessed by Shannon index, did not differ significantly among children from 5 through 13 weeks after birth, but thereafter gradually increased to 21 and 31 weeks. Most bacteria within the Bacteroidetes and Proteobacteria phyla were already present at 5 weeks after birth, whereas many bacteria of the Firmicutes phylum were acquired at later times in infancy. At school age, many new Actinobacteria, Firmicutes, and Bacteroidetes bacterial taxa emerged. The largest increase in microbial diversity occurred after 31 weeks. Vaginal, compared with cesarean delivery, was most strongly associated with an enrichment of Bacteroides species at 5 weeks through 31 weeks. From 13 weeks onward, diet became the most important determinant of microbiota composition; cessation of breastfeeding, rather than solid food introduction, was associated with changes. For example, Bifidobacteria, staphylococci, and streptococci significantly decreased on cessation of breastfeeding, whereas bacteria within the Lachnospiraceae family (Pseudobutyrivibrio, Lachnobacterium, Roseburia, and Blautia) increased. When we adjusted for confounding factors, we found fecal microbiota composition to be associated with development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy. In a longitudinal study of fecal microbiota of children from 5 weeks through 6 to 11 years, we tracked changes in diversity and composition associated with the development of allergies and asthma.

Galazzo G ，van Best N ，Bervoets L ，Dapaah IO ，Savelkoul PH ，Hornef MW ，GI-MDH consortium ，Lau S ，Hamelmann E ，Penders J ... -  《-》