Project description:Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNAseq of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later – or not at all – showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early life microbiome in later life dysmotility.
Project description:BackgroundTriclosan exposure may decrease circulating thyroxine levels or cause neuron apoptosis, which in turn may adversely affect neurodevelopment. However, few studies have examined the association of early life triclosan exposure with child behavior.ObjectiveTo quantify the association between early-life triclosan exposure and child behavior at age 8-years in 202 mother-child pairs from the HOME study (Cincinnati, OH; enrolled: 2003-2006).MethodsWe quantified urinary triclosan concentrations up to 3 times in mothers (16-weeks, 26-weeks, and delivery) and up to 6 times in children (1, 2, 3, 4, 5, and 8 years). Parents rated children's problem behaviors at age 8-years using the Behavioral Assessment System for Children-2 (BASC-2). Adjusting for covariates and accounting for exposure measurement error, we estimated changes in behavior problem scores per 10-fold increase in mean gestational and childhood triclosan concentrations. In addition, we estimated sex-specific associations.ResultsChild sex modified the association of gestational and childhood triclosan with several BASC-2 scales (sex × triclosan p-values < 0.2). In boys, increasing gestational triclosan was associated with higher behavioral symptom index (β: 4.5; 95% CI: 1.0, 8.1), externalizing problems (β: 5.0; 95% CI: 1.2, 9.0), attention problem (β: 6.6; 95% CI: 2.4, 11), hyperactivity (β: 6.4; 95% CI: 2.1, 11), and somatization (β: 3.8; 95% CI: 0.3, 7.3) scores. In contrast, triclosan-BASC-2 associations in girls were generally null and not statistically significant. We observed similar patterns of associations between childhood triclosan and these same behavioral scores; however, their magnitude decreased substantially after adjusting for gestational triclosan and associations were not statistically significant.ConclusionIn this cohort, increasing gestational and childhood urinary triclosan concentrations were associated with higher behavior problem scores in 8-year old boys, but not girls.
Project description:BackgroundThe gut microbiota has been associated with overweight and obesity in adults, but the evidence in children is limited. Our aim was to study whether composition of the gut microbiota at the age of 3 years is associated with overweight/obesity in children cross-sectionally.MethodsChildren, who participated in a clinical trial of prenatal vitamin-D supplementation (VDAART), underwent standardized height and weight measurements, and collection of stool samples at 3 years of age. 16 S rRNA sequencing (V4 region) of the stool samples were performed with Illumina MiSeq. Associations between microbiota and overweight/obesity (body mass index z-scores >85th percentile) was analyzed using logistic regression.ResultsOut of 502 children, 146 (29%) were categorized as overweight/obese. Maternal pre-pregnancy BMI, birth weight and length, formula feeding during the first year, high frequency of fast food consumption, and time watching TV or computer screen at 3 years were the risk factors for overweight/obesity. Of the top 20 most abundant genera, high relative abundance of Parabacteroidetes (Bacteroidetes; Bacteroidales) (aOR(95% CI): 0.69 (0.53, 0.90, p = 0.007) per interquartile increase) and unassigned genus within Peptostreptococcae family were inversely associated with overweight/obesity, whereas high relative abundance of Dorea (Firmicutes;Clostridiales) (1.23 (1.05, 1.43, p = 0.009)) was positively associated. Associations were independent of each other. No associations were found between diversity indices and overweight/obesity.ConclusionsOur data suggest that some of the differences in gut composition of bacteria between obese and non-obese adults can already be observed in 3-year old children. Longitudinal studies will be needed to determine long-term effects.
Project description:BACKGROUND:To identify modifiable antecedents during pre-pregnancy and pregnancy windows associated with a positive child health at 10 years of age. METHODS:Data on 889 children enrolled in the Extremely Low Gestational Age Newborn (ELGAN) study in 2002-2004 were analyzed for associations between potentially modifiable maternal antecedents during pre-pregnancy and pregnancy time windows and a previously described positive child health index (PCHI) score at 10 years of age. Stratification by race was also investigated for associations with investigated antecedents. RESULTS:Factors associated with higher PCHI (more positive health) included greater gestational age, birth weight, multiple gestation, and medical interventions, including assisted reproduction and cervical cerclage. Factors associated with lower PCHI included correlates of lower socioeconomic status, pre-pregnancy chronic medical disorders in the mother such as pre-pregnancy body mass index (BMI), and maternal asthma. When stratified by race, variation in significant results was observed. CONCLUSIONS:Among children born extremely preterm, medical interventions and higher socioeconomic status were associated with improved PCHI, while chronic illness and high BMI in the mother is associated with lower PCHI at 10 years of age. Knowledge of such antecedent factors could inform efforts to develop interventions that promote positive child health outcomes in future pregnancies.
Project description:While the association between early life determinants and the development of the gut microbiome composition in infancy has been widely investigated, a potential persistent influence of early life determinants on the gut microbial community after its stabilization at later childhood remains largely unknown. Therefore, we aimed to identify the association between several early life determinants and the gut microbiome composition in six-year-old children from the LISA birth cohort. A total number of 166 fecal samples were analyzed using 16S rRNA gene-based barcoding to assess bacterial diversity pattern. The bacterial profiles were investigated for their association with maternal smoking during pregnancy, mode of delivery, breastfeeding, antibiotic treatment between one and two years of age, gender and socioeconomic status (SES). While alpha and beta diversity of the infants' gut microbiome remained unaffected, amplicon sequence variants (ASVs) annotated to Firmicutes and Actinobacteria responded to early life determinants, mostly to feeding practice and antibiotics use. ASVs associated to Bacteriodetes remained unaffected. Our findings indicate that early life determinants could have a long-term sustainable effect on the gut microflora of six-year-old children, however, associations with early life determinates are weaker than reported for infants.
Project description:We studied the association of early-life environmental and child factors with disruptive behaviors in children with autistic traits around age 7, in the Avon Longitudinal Study of Parents and Children (n = 6,401). Logistic regression with the least absolute shrinkage and selection operator indicated that disruptive behaviors were associated with prenatal smoking, no seafood-consumption during pregnancy, breech presentation at delivery, neonatal feeding problems, low social-economic situation, suboptimal preschool family environment, maternal depression, maternal antisocial behavior, male sex, and difficult child temperament. Compared to controls, male sex, maternal depression, and suboptimal preschool family environment were related to autistic traits without disruptive behaviors. Thus, there may be a difference in early-life factors related to autism spectrum disorder with and without disruptive behaviors.