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

Atara Uzan-Yulzari,Hanna Lagström,Anne Kaljonen,Hila Ben-Amram,Aia Oz,Oren Ziv,Hadar Neuman,Edoardo Pasolli,Nicola Segata,Itai Sharon,Helena Ollila,Seppo Salminen,Samuli Rautava,Anna Belogolovski,Erika Isolauri,Sarah Perschbacher,Himanshu Kumar,Yoram Louzoun,Olli Turta,Christina Kunz,Regina Ensenauer,Omry Koren

doi:10.1038/s41467-020-20495-4

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.

Highlights

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development
The impact of neonatal antibiotic exposure on growth during the first six years of life was first investigated in the Southwest Finland Birth Cohort (SFBC) consisting of all 14,969 children born at the Turku University Hospital in Turku, Finland during the years 2008–2010
12,422 children born from singleton pregnancies at full term who did not have genetic abnormalities or significant chronic disorders affecting growth and who did not need long-term prophylactic antibiotic treatment were included in this study

Summary

Introduction

Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. 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. 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. Experimental studies using germ-free mice demonstrate that fecal microbiota transplant (FMT) with fecal samples from infants exposed to antibiotics in the neonatal period results in growth failure in male but not in female mice, which suggests a causal role for the antibiotic-induced gut microbiome perturbations in the pathogenesis of the growth impairment in antibiotic-exposed boys

Methods

Results

Conclusion