Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization

Abstract

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.

Weight shapes the intestinal microbiome in preterm infants: results of a prospective observational study

“…Important in this regard is to again note that bifidobacteria or lactobacilli are generally absent in extremely premature children. The abundance, or the diminished abundance in the case of antibiotics [37], of these bacteria is frequently linked with improved growth. Similarly, the use of probiotics in term and preterm infants has been found associated with improved weight gain [38].…”

Early-life gut microbiota and its connection to metabolic health in children: Perspective on ecological drivers and need for quantitative approach

“…Uzan-Yulzari et al recently reported that neonatal antibiotic exposure was associated with reduced growth during the first six years of life particularly in boys, whereas antibiotic use after the neonatal period was associated with excessive childhood weight gain in both genders. These effects were likely mediated by the gut microbiota, specifically the decreased abundance and diversity of bifidobacteria, which remained detectable even 24 months after exposure [85]. Alarmingly, antibiotic exposure during the breastfeeding period may eliminate the beneficial metabolic effects of breastfeeding by altering the gut microbiota [86].…”

Early Life Microbial Exposure and Immunity Training Effects on Asthma Development and Progression

“…In addition to mode of delivery, the antibiotics usage during the pregnancy seems alter both the maternal and neonatal microbiomes which may lead to subsequent allergy diseases in childhood ( 16 , 17 ). Moreover, evidence suggesting that maternal antibiotic usage before and after pregnancy can increase the childhood asthma's risk ( 18 ). Furthermore, it should be noted that child exposed to antibiotics in the first days of life can reduced abundance and diversity of Bifidobacterium species ( 18 ) and increase the abundancy of Enterobacteriaceae species ( 19 ), which may induce the development of asthma.…”

“…Moreover, evidence suggesting that maternal antibiotic usage before and after pregnancy can increase the childhood asthma's risk ( 18 ). Furthermore, it should be noted that child exposed to antibiotics in the first days of life can reduced abundance and diversity of Bifidobacterium species ( 18 ) and increase the abundancy of Enterobacteriaceae species ( 19 ), which may induce the development of asthma. Therefore, it is important to raise the question about the contributions of antibiotics and infection on microbiome disturbance during and after pregnancy, further studies regarding this topic should be address.…”