Antibiotic exposure prevents acquisition of beneficial metabolic functions in the preterm infant gut microbiome

Abstract

Background Aberrations in the preterm microbiome following antibiotic therapy have been reported in previous studies. The objective of this study was to probe potential underlying mechanisms between this observation and susceptibility to adverse prematurity-related outcomes. Results Metagenomic shotgun sequencing was performed on 133 stool and 253 skin samples collected at 1 and 3 weeks of age from 68 infants born at <36 weeks postmenstrual age and birth weight <2000 g. After accounting for gestational age and maternal antibiotics, the distribution of organisms in all samples and the corresponding metabolic pathway abundance were compared between infants exposed to postnatal antibiotics and antibiotics-naïve infants. In antibiotic-naïve infants, gestational and postnatal age imparted similar trajectories on maturation of the microbial community and associated metabolic functional capacity, with postnatal age exerting greater contribution. Antibiotic exposure was associated with reversal in maturation trajectory from the first week to the third week of age (p< 0.001). Butyrate-producing genera, including Clostridium and Blautia, were significantly more abundant in antibiotic-naïve neonates at 3 weeks postnatal age. Correspondingly, metabolic pathways required for short-chain fatty acid synthesis were significantly increased in antibiotic-naïve infants, but not in antibiotic-exposed neonates, at 3 weeks after birth. Conclusions Early brief antibiotic exposure markedly disrupts developmental trajectory of the neonatal microbiome and its corresponding functional capacity. Our findings may provide a mechanistic explanation for the known associations between antibiotic use and adverse outcomes in preterm infants.

Early antibiotics and risk for necrotizing enterocolitis in premature infants: A narrative review

“…In another study, gut colonization of mice with the symbiotic bacteria Bacteroides fragilis was found to mediate establishment of proper Th1/Th2 balance through bacterial surface polysaccharide A (62). Disruptions to this normal process of gut colonization with commensalssuch as with early antibiotic usecan thus lead to a dysfunctional gut mucosa predisposed to NEC(64)(65)(66). This hypothesis is supported by the mouse model by Chaaban et al (50) where exposure of newborn pups to 10 days of antibiotics resulted in several impairments to gut mucosal barrier, intestinal permeability, intestinal stem cell proliferation, and Paneth cell function.…”

Restrictive Use of Empirical Antibiotics Is Associated with Improved Short Term Outcomes in Very Low Birth Weight Infants: A Single Center, Retrospective Cohort Study from China

“…Saleem et al [ 24 ] have demonstrated that the longer the duration of antibiotic use in preterm infants, the greater the delay in their feeding. Many scholars now believe that early antibiotic use in VLBW infants can lead to intestinal flora dysbiosis [ 25 , 26 ], which increases the risk of adverse outcomes such as NEC [ 27 ], prolongs the length of hospitalization, and increases the medical costs in preterm infants. In this study, the time to reach full enteral nutrition was also reduced significantly over the initial 3 years of the study period, suggesting that shortening the duration of early empirical antibiotic therapy may facilitate the establishment of normal intestinal flora and therefore decrease the time to reach full enteral feeds, and subsequently the incidence of LOS.…”

Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis

“…Difference in species abundance between individuals with normal vs elevated L:R were identified with shrinkage linear discriminant analysis. 67 Significance of the association was tested using Wilcoxon rank sum. Examination of clinical covariates with microbial abundance was performed using zero inflated negative binomial generalized linear mixed models (ZINB-GLMM 68 ) using the “glmer” command from the lme4 package in R and performed nonparametric tests (Mann-Whitney U test or Kruskal-Wallis test), followed by Bonferroni correction for multiple testing.…”