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Background and Aims Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children. Methods In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted. Results Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13–7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75–22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization. Conclusions This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort. Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months. Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota. This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.

Background & Aims Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. Methods: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. Results After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. Conclusions Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

OBJECTIVES: Colonization with Clostridioides difficile occurs in up to half of infants and is predicted by formula feeding. Although this microbe does not appear to pose any immediate risks for infants, its presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting changes in the gut microbiome that may increase opportunity for colonization of pathogenic bacteria. We explored these compositional changes in exclusively breastfed, partially breastfed and exclusively formula fed infants to describe the microbial community and C. difficile colonization in infants with distinct diets. METHODS: This study includes 1562 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. Infants provided a fecal sample at 3–4 months of age (Mean: 3.56, SD: 1.00) which was analyzed using 16S rRNA sequencing and targeted qPCR for C. difficile. Mode of feeding was recorded in a questionnaire at a 3 month follow-up visit. C. difficile colonization was defined as positive detection (CD+) in the fecal sample (reference: not present, CD-). Multivariate association with linear models (MaAslin) was used to determine changes in microbiota composition following arsine-square root transformation of relative abundances and FDR correction. RESULTS: The prevalence of C. difficile colonization among all infants was 30.9%. Colonization rates differed among feeding groups: 22.63% of exclusively breastfed infants, 35.96% of partially breastfed infants and 49.63% of exclusively formula fed infants (P

BACKGROUND: Emerging links between household cleaning products and childhood overweight may involve the gut microbiome. We determined mediating effects of infant gut microbiota on associations between home use of cleaning products and future overweight. METHODS: From the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort, we tested associations between maternal report of cleaning product use and overweight at age 3, and whether associations were mediated by microbial profiles of fecal samples in 3- to 4-month-old infants. RESULTS: Among 757 infants, the abundance of specific gut microbiota was associated with household cleaning with disinfectants and eco-friendly products in a dose-dependent manner. With more frequent use of disinfectants, Lachnospiraceae increasingly became more abundant (highest v. lowest quintile of use: adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.08 to 3.45) while genus Haemophilus declined in abundance (highest v. lowest quintile of use: AOR 0.36, 95% CI 0.20 to 0.65). Enterobacteriaceae were successively depleted with greater use of eco-friendly products (AOR 0.45, 95% CI 0.27 to 0.74). Lachnospiraceae abundance significantly mediated associations of the top 30th centile of household disinfectant use with higher body mass index (BMI) z score (p = 0.02) and with increased odds of overweight or obesity (p = 0.04) at age 3. Use of eco-friendly products was associated with decreased odds of overweight or obesity independently of Enterobacteriaceae abundance (AOR 0.44, 95% CI 0.22 to 0.86), with no significant mediation (p = 0.2). INTERPRETATION: Exposure to household disinfectants was associated with higher BMI at age 3, mediated by gut microbial composition at age 3–4 months. Although child overweight was less common in households that cleaned with eco-friendly products, the lack of mediation by infant gut microbiota suggests another pathway for this association.

Importance The effect of neonatal and infant feeding practices on childhood obesity is unclear. The gut microbiome is strongly influenced by feeding practices and has been linked to obesity. Objective To characterize the association between breastfeeding, microbiota, and risk of overweight during infancy, accounting for the type and timing of supplementary feeding. Design, Setting, and Participants In this study of a subset of 1087 infants from the prospective CHILD pregnancy cohort, mothers were recruited between January 1, 2009, and December 31, 2012. Statistical analysis was performed from February 1 to December 20, 2017. Main Outcomes and Measures Feeding was reported by mothers and documented from hospital records. Fecal microbiota at 3 to 4 months (from 996 infants) and/or 12 months (from 821 infants) were characterized by 16S ribosomal RNA sequencing. Infants with a weight for length exceeding the 85th percentile were considered to be at risk for overweight. Results There were 1087 infants in the study (507 girls and 580 boys); at 3 months, 579 of 1077 (53.8%) were exclusively breastfed according to maternal report. Infants who were exclusively formula fed at 3 months had an increased risk of overweight in covariate-adjusted models (53 of 159 [33.3%] vs 74 of 386 [19.2%]; adjusted odds ratio, 2.04; 95% CI, 1.25-3.32). This association was attenuated (adjusted odds ratio, 1.33; 95% CI, 0.79-2.24) after further adjustment for microbiota features characteristic of formula feeding at 3 to 4 months, including higher overall richness and enrichment of Lachnospiraceae. A total of 179 of 579 infants who were exclusively breastfed (30.9%) received formula as neonates; this brief supplementation was associated with lower relative abundance of Bifidobacteriaceae and higher relative abundance of Enterobacteriaceae at 3 to 4 months but did not influence the risk of overweight. At 12 months, microbiota profiles differed significantly according to feeding practices at 6 months; among partially breastfed infants, formula supplementation was associated with a profile similar to that of nonbreastfed infants (higher diversity and enrichment of Bacteroidaceae ), whereas the introduction of complementary foods without formula was associated with a profile more similar to that of exclusively breastfed infants (lower diversity and enrichment of Bifidobacteriaceae and Veillonellaceae ). Microbiota profiles at 3 months were more strongly associated with risk of overweight than were microbiota profiles at 12 months. Conclusions and Relevance Breastfeeding may be protective against overweight, and gut microbiota may contribute to this effect. Formula feeding appears to stimulate changes in microbiota that are associated with overweight, whereas other complementary foods do not. Subtle microbiota differences emerge after brief exposure to formula in the hospital. These results identify important areas for future research and distinguish early infancy as a critical period when transient gut dysbiosis may lead to increased risk of overweight.

It has been just over three centuries since Antonie van Leewenhoek first conclusively documented the biological nature of the elements of air and dust in the built environment [1]. During the 20th century, advancements in sampling instrumentation and analysis techniques yielded a large literature on the microbiology of air and dust, mainly using culture and microscopy [2, 3]. In the past few decades, the measurement of health-relevant biochemicals such as allergens, endotoxin, and glucan in the context of population health studies has contributed substantially to our understanding of how the built environment can influence health. In the past few years, investigations of the built environment using culture-independent sequence-based analysis have confirmed many previously held expectations about the sources and fates of indoor microbes, and in the process, these methods have also produced several unexpected insights into the indoor microbiome. Perhaps not surprisingly, the biological composition of air and dust appears to be vastly more complex than formerly thought. Over the next decade, molecular metagenomic methods are likely to revolutionize our understanding of the roles of air and dust in the biology of life on earth, and in the process, provide sophisticated new tools to elucidate health-environment interactions. This review summarizes recent key studies on the microbiology of the built environment to date using modern culture-independent methods, and considers the implications of these findings and future studies elucidating the interactions between the humans and the built environment.

Asthma during pregnancy is associated with retardation of fetal growth in a sex-specific manner. Lactobacilli microbes influence infant growth. This study aimed to determine whether lactobacilli and other microbes are reduced in the gut of infants born to an asthmatic mother, and whether this differs by the sex of the infant. Mother-infant pairs (N=1021) from the Canadian Healthy Infant Longitudinal Development full-term cohort were studied. The abundance of infant faecal microbiota at 3–4 months, profiled by gene sequencing, was compared between both women with and without asthma treatment during pregnancy. Infant sex, maternal ethnicity, pre-pregnancy overweight and atopy status, birth mode, breastfeeding status and intrapartum antibiotic treatment were tested as covariates. Independent of birth mode and other covariates, male, Caucasian infants born to women with prenatal asthma harboured fewer lactobacilli in the gut at 3–4 months of age. If asthmatic mothers had pre-pregnancy overweight, the abundance of Lactobacillus in males was further reduced in the infant gut, whereas the microbiota of female infants was enriched with Bacteroidaceae. Similar differences in infant gut microbial composition according to maternal prenatal asthma status were also more evident among women with food or environmental allergies. Gut lactobacilli were less abundant in male infants, but Bacteroidaceae were more abundant in female infants at 3–4 months of age, following maternal asthma during pregnancy., Gut lactobacilli are less abundant at 3–4 months in male but not female infants following maternal prenatal asthma http://ow.ly/jXnl30fU9xH

RATIONALE: Breastfeeding may be protective against obesity, but existing evidence is inconsistent. The gut microbiota, which itself is shaped by breastfeeding and other early-life exposures, may also contribute to the development of obesity. OBJECTIVE: To determine whether breastfeeding is protective against early childhood overweight, and to explore related associations with the gut microbiota. METHODS: The study involved 346 full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) national birth cohort. Mothers reported breastfeeding by standardized questionnaire, and child overweight was defined by weight-for-length z-score (WFLz) according to World Health Organization standards. In a subset of 158 infants, the gut microbiota was characterized by Illumina 16S rRNA sequencing of fecal samples collected at 3 months. RESULTS: Breastfeeding rates (any breastfeeding) were 81%, 73%, and 46% at 3, 6 and 12 months, respectively. By 12 months, 16% of children were at risk for overweig...

Background Disruption of the infant gut microbiota has been linked to long-term health outcomes, including obesity and allergic disease [1]. Antibiotics can significantly alter the microbiota [2], but evidence is scarce for the long-term effect of antibiotic exposure during the perinatal period (shortly before or after delivery). Our research aimed to determine the impact of infant and maternal perinatal antibiotic exposure on the infant gut microbiota at 1 year of age.

Background Inverse associations between allergic disease and having pets or siblings are commonly attributed to the hygiene hypothesis. As an extension, one could posit that a less diverse gut microbiome in the infant, also linked with the development of allergic disease, would be a function of fewer microbes in the home environment. Piglet studies, however, indicate that greater microbe diversity in the environment actually leads to reduced diversity of the gut microbiota. In this study, we characterize the infant gut microbiota in relation to environmental factors traditionally associated with the hygiene hypothesis.

Background Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings. Methods The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing. Results Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae. Conclusions This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.

Methods The study comprised a sub-sample of 190 healthy term infants from one centre participating in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study. Mode of delivery was determined from hospital records, and mothers reported infant diet at 3, 6 and 12 months postpartum. Antibiotic exposure was documented from hospital and prescription records. Gut microbiota was characterized by Illumina 16S rRNA sequencing of fecal samples collected at 12 months.