Birth mode and infant gut microbiota sequentially mediate the association of maternal overweight with childhood overweight

摘要

Background: Childhood overweight is a global public health concern. In Canada, over 20% of preschool children are overweight. Also on the rise is maternal obesity during pregnancy. Although children born to obese mothers are at higher risk for obesity, the mechanisms behind this association are not fully delineated. The transmission of obesogenic microbiota is recently hypothesized as a novel possible pathway. The current study examined whether birth mode and infant gut microbial diversity are sequential mediators in the association between maternal and childhood obesity. Methods: The study population comprised a large sub-sample of 999 infants enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) population-based birth cohort. Maternal BMI [body mass index = weight (kg)/height (m )] was calculated from data taken from hospital records or pre-pregnancy recall, or measurements taken at 1 year if the former were not available. Maternal overweight/obesity was classified as > BMI 25.0. Gut microbial diversity and composition of 3-month old infants was assessed using high-throughput 16S rRNA sequencing. At age 3 years, age-gender BMI-z scores were generated from measured weight and height according to WHO criteria. Child overweight/ obesity was defined as >97th centile BMI z score. Data on maternal smoking, birth mode, breastfeeding and antibiotic exposure were retrieved from administered questionnaires or birth charts. A multiple mediator path model was evaluated to examine the indirect effects of birth mode (M1) and infant gut microbial diversity (M2) as mediators of the maternal -childhood obesity association. Statistical analyses were performed in SAS V9.4. Results: One in 5 toddlers born to overweight/obese mothers were overweight at age 3 years versus 5% of children born to normal weight mothers. This translated into a 5-fold increased risk of overweight/obese at age 3 years (OR: 4.9, 95%CI: 2.8-8.7). Maternal overweight was associated with increased infant gut microbial indices at 3 months of age including total microbiota species richness, Firmicutes richness and diversity (P < 0.01). Increases in these indices elevated risk of overweight in toddlers more than two times. Moreover, overweight mothers were more likely to give birth by CS (OR 1.4, 95%CI: 1.1-1.9). CS-delivered infants had high total microbiota species richness but low Firmicutes richness and diversity at 3 months (P < 0.05). The multiple mediator path modeling revealed that birth mode and infant gut microbiota (especially total species and Firmicutes richness) sequentially mediated the association of maternal overweight with childhood overweight (P < 0.05). Conclusion: This study provides evidence of a novel sequential mediator pathway involving mode of delivery and infant gut microbiota for the association between maternal overweight and childhood overweight.