Effects of One-Week Empirical Antibiotic Therapy on the Early Development of Gut Microbiota and Metabolites in Preterm Infants

Danping Zhu,Chen Cheng,Yun Pan,Yunhui Zhang,Yu He,Jialin Yu,Qing Ai,Sa Xiao

doi:10.1038/s41598-017-08530-9

Abstract

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Highlights

Reports of association of prolonged initial empirical antibiotic treatment with late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death in preterm infants[9, 10]
We explored the changes in gut bacterial communities and metabolites in preterm neonates following one-week treatment with different combinations of β-lactam related antibiotics in comparison with antibiotic-free controls
It has been reported that a decrease in the diversity of gut microbiota could be detected at week one and week two after stopping a less than three days antibiotic treatment in infants, but at week three, the microbial diversity in these infants was restored to the same level as week one[11, 18]

Summary

Introduction

Reports of association of prolonged initial empirical antibiotic treatment with late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death in preterm infants[9, 10]. Several studies suggested that a decrease in the microbiota diversity in the first seven postnatal days may lead to asthma and eczema during childhood[13,14,15]. It is unknown how prolonged use of antibiotics affect the gut microbiota during this period. Among the most commonly prescribed antibiotics to preterm babies are the broad-spectrum β-lactam antibiotics, which contain a β-lactam ring in their molecular structures. This class of antibiotics includes penicillin and its derivatives (such as piperacillin, monobactams, cephalosporins, and carbapenems). We examined the differences in gut bacterial community and their metabolites between preterm infants receiving different antibiotics, including the combination of penicillin-moxalactam (PM group) and piperacillin-tazobactam (PT group)

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