Built Environment, Microbiota and Asthma at Age 3: Longitudinal Follow-Up in a Canadian Birth Cohort

摘要

Background The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort was designed to define factors related to the development of asthma. We examined modifiable environmental exposures and gut microbiota with respect to asthma incidence. Methods Stool samples collected at 3 and 12 months from an asthma-enriched CHILD subset (n=999) were profiled with 16S rRNA sequencing. Mothers' built environment was assessed at their residential addresses with a satellite measure of greenness (NDVI) and land use regression models to derive nitrogen dioxide (NO2) individual estimates of traffic-related air pollution (TRAP). Data were collected on intrinsic risk factors, including parental asthma status, mode of delivery, parity, socio-economic factors, and antibiotic use. We examined the association of gut microbiota composition with environmental factors and their impact on asthma at age 3yrs. Results Children with asthma at 3 years (n=312) had higher exposure to N02 (mean (SD): 16.1 (7.2) ppb)) and lower exposure to greenness (NDVI mean (SD): 0.25 (0.08)) compared to those without asthma (NO2: (14.7 (6.8) ppb); NDVI: 0.26 (0.08)). Children with asthma were more likely to have atopic primiparous mothers who were prescribed antibiotics during pregnancy. While microbiome alpha diversity increased between 3 months and 1 year, maternal atopy (p=0.06) and prenatal TRAP exposure (p=0.05) were negatively associated with this trend. Infants diagnosed with asthma by 3yrs had different microbiota composition at 3 months (p=0.002), including reduced Oscillospira colonization (FDR p<0.05). Prenatal TRAP exposure also accompanied shifts in beta-diversity at 3 months (p=0.002) and was negatively correlated with Oscillospira abundance (spearman r=-.13; FDR p<0.01). Conclusions Increased alpha diversity and Oscillospira abundance-known health protective features of the microbiota-were negatively associated with TRAP which is a key modifiable environmental risk factor.