Exposure to tobacco smoke in prenatal and early postnatal life alters infant gut microbiota and increases risk of childhood overweight

摘要

Background: Globally, the prevalence of overweight in children has increased over the past three decades. The association between smoking during pregnancy and overweight in offspring has been reported in a number of studies and confirmed by recent meta-analyses. However, most studies focus only on maternal smoking and fail to adjust for smoking of other household members. Long term exposure to cigarette smoke induces changes in microbial composition and inflammation in the gut of both adult human and mice. In this study, we investigate the effect of household tobacco smoke exposure in prenatal and early postnatal periods on the infant gut micro-biota composition and overweight risk at ages 1 and 3. Methodology: The study population comprised a large sub-sample of 999 infants enrolled at the Edmonton, Vancouver and Winnipeg sites of the Canadian Healthy Infant Longitudinal Development (CHILD) population-based birth cohort. Smoking exposure status (both maternal and other household members) was collected in both prenatal and postnatal questionnaires and categorized into four groups: no exposure (n = 791, 78.2%); exposure only during pregnancy (n= 15, 1.5%); exposure only postnatally (n = 107,10.7%); and exposure during pregnancy and postnatally (n = 46, 4.6%). At 1 and 3 years old, weight and height of infants were measured, and age and sex adjusted weight-for-length and BMI (body mass index) z scores were generated according to the WHO criteria. Children with a weight-for-length or BMI z score > 97th centile were classified as overweight/obese. Gut microbial diversity and composition of infants at 3-4 months after birth was assessed using high-throughput 16 S rRNA sequencing. Maternal overweight/obesity (classified as BMI >25.0) was considered as a main covariate for childhood obesity. Other covariates, including ethnicity, mode of delivery, infant sex, breastfeeding, antibiotics exposure and presence of siblings were retrieved from standardized questionnaires completed by mothers. The mediation effect of microbiota measurements was evaluated. Statistical analyses were performed in SAS V9.4. Results: Exposure to tobacco smoke postnatally only, or during both the pregnancy and postnatal periods, was significantly associated with overweight/obesity at age 1 year (OR: 2.10, 95%CI: 1.13-3.91, and OR: 3.32, 95%CI: 1.42-7.75, respectively) and 3 years (OR: 2.79, 95%CI: 1.46-5.32, and OR: 3.61, 95%CI: 1.36-9.60, respectively). However, the association for household smoke exposure during pregnancy and postnatally was attenuated when adjusted for maternal prenatal smoking. Species richness of Firmicutes and abundance of Ruminococcaceae at 3 months of age was significantly increased in infants exposed to tobacco smoke postnatally or both pre and postnatally (P<0.05). Independent to tested covariates, the highest tertile of Firmicutes richness provided a two-fold higher risk of overweight/obesity at age 1 and 3 (aOR: 2.28, 95%CI: 1.29-4.01, and aOR: 1.91, 95%CI: 1.01-3.60, respectively). A mediation analysis revealed potential mediation by gut microbiota, especially Firmicutes richness, in the association between postnatal smoking exposure and the risk of childhood overweight at age 1 and 3 (Bootstrap 95%CI: 0.01-0.13, and 95%CI: 0.01-0.09, respectively). Conclusion: Our study highlights that exposure to household tobacco smoking in early life can alter infant gut microbiota at 3-4 months and may increases risk of childhood overweight and obesity.