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

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.

Probiotic Supplementation during the Perinatal and Infant Period: Effects on gut Dysbiosis and Disease

“…From the 434 screened studies related to this topic, 15 potentially eligible articles met the pre-established inclusion criteria, including the use of 16S rRNA gene sequencing methodology to analyze biological samples ( Table 1). All studies reported on the antibiotic-induced impact on the composition of neonatal gut microbiota, but treatment options differed between studies: seven studies had mothers receiving intrapartum antibiotics (IPA) [12,[60][61][62][63][64][65] five studies focused on postnatal antibiotic therapy [10,[66][67][68][69]. A further two studies assessed pre and postnatal antibiotic therapy: Zou et al analyzed the effects of prenatal antibiotic exposure and the intensity of prenatal and postnatal antibiotic exposure on gut microbiota of preterm infants [70].…”

“…Arboleya et al evaluated the effects of IPA and postnatal antibiotics administered in the first week versus the second week of life [72]. Six studies reported a decrease in microbial diversity induced by antibiotics [10,62,[64][65][66]71], while three studies showed no statistically significant differences between the antibiotic exposure and antibiotic-free groups [67,69,70]. Low microbial diversity indices were associated with NEC and a high risk of obesity and inflammatory diseases [73].…”

“…Low microbial diversity indices were associated with NEC and a high risk of obesity and inflammatory diseases [73]. Regarding microbial composition, eight studies highlighted increased colonization rates of Enterobacteriaceae [10,60,62,65,67,69,70,72], a risk factor for necrotizing enterocolitis (NEC) and sepsis, especially in the preterm population. Both IPA and postnatal antibiotic therapy also showed an impact on protective phylum Bacteroidetes (eight studies) [60,64,66,67,[69][70][71][72], which provides colonization resistance against antibiotic-resistant bacteria and pathogenic bacteria (Enterobacteriaceae and Clostridium difficile) [74,75].…”

“…Regarding microbial composition, eight studies highlighted increased colonization rates of Enterobacteriaceae [10,60,62,65,67,69,70,72], a risk factor for necrotizing enterocolitis (NEC) and sepsis, especially in the preterm population. Both IPA and postnatal antibiotic therapy also showed an impact on protective phylum Bacteroidetes (eight studies) [60,64,66,67,[69][70][71][72], which provides colonization resistance against antibiotic-resistant bacteria and pathogenic bacteria (Enterobacteriaceae and Clostridium difficile) [74,75]. Further reduced colonization rates of Bifidobacteriaceae were reported in twelve studies [60][61][62][63]65,[67][68][69][70][71][72]76] and Actinobacteria in six studies [60,[62][63][64]67,72].…”

“…Both IPA and postnatal antibiotic therapy also showed an impact on protective phylum Bacteroidetes (eight studies) [60,64,66,67,[69][70][71][72], which provides colonization resistance against antibiotic-resistant bacteria and pathogenic bacteria (Enterobacteriaceae and Clostridium difficile) [74,75]. Further reduced colonization rates of Bifidobacteriaceae were reported in twelve studies [60][61][62][63]65,[67][68][69][70][71][72]76] and Actinobacteria in six studies [60,[62][63][64]67,72]. Nine studies showed an increase in Proteobacteria [60,[62][63][64]66,67,69,70,72] colonization which is a marker of an unstable microbial community, especially when associated with decreased levels of the phylum Firmicutes [77].…”