Abstract
BackgroundThe ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% in 1099 infants born before 32 completed weeks’ gestation and weighing < 1500 g, receiving probiotic supplementation (with Bifidobacterium longum subsp. infantis BB-02, Streptococcus thermophilus TH-4 and Bifidobacterium animalis subsp. lactis BB-12). This sub-study investigated the effect of probiotic supplementation on the gut microbiota in a cohort of very preterm infants in ProPrems.ResultsBifidobacterium was found in higher abundance in infants who received the probiotics (AOR 17.22; 95% CI, 3.49–84.99, p < 0.001) as compared to the placebo group, and Enterococcus was reduced in infants receiving the probiotic during the supplementation period (AOR 0.27; 95% CI, 0.09–0.82, p = 0.02).ConclusionProbiotic supplementation with BB-02, TH-4 and BB-12 from soon after birth increased the abundance of Bifidobacterium in the gut microbiota of very preterm infants. Increased abundance of Bifidobacterium soon after birth may be associated with reducing the risk of NEC in very preterm infants.
Highlights
The ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% in 1099 infants born before 32 completed weeks’ gestation and weighing < 1500 g, receiving probiotic supplementation
A large multicenter study of 1315 preterm infants found no reduction in the incidence of NEC following supplementation with a single-strain probiotic. This could suggest that not all probiotics have equivalent efficacy in preventing NEC and further work is needed to better understand how and why some probiotic combinations work and others do not. In this sub-study, we investigated the effect of probiotic supplementation on the development of the gut microbiota of preterm infants by examining the gut bacterial communities in a cohort of very preterm infants enrolled in the ProPrems trial [19]
No difference in effective number of genera was observed between the probiotic and placebo groups. This sub-study investigated the effect of probiotic supplementation with B. longum subsp. infantis BB-02, S. thermophilus TH-4 and B. animalis subsp. lactis BB-12 on the gut microbiota of a subset of very preterm infants enrolled in the ProPrems trial and found that infants supplemented with probiotics had a higher abundance of Bifidobacterium compared to control infants
Summary
The ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% in 1099 infants born before 32 completed weeks’ gestation and weighing < 1500 g, receiving probiotic supplementation (with Bifidobacterium longum subsp. infantis BB-02, Streptococcus thermophilus TH-4 and Bifidobacterium animalis subsp. lactis BB-12). Preterm infants have a different gut microbiota than term newborns, including reduced species diversity, higher numbers of Enterobacteriaceae (including Klebsiella pneumoniae and Escherichia coli) and Clostridium difficile, and reduced numbers of Bifidobacteria and Lactobacilli [2, 3] These differences may be a result of host factors associated with immaturity as well as various environmental factors including delivery mode, reduced exposure to maternal microbiota, Necrotizing enterocolitis is a devastating inflammatory disease of the intestine that affects approximately 7% of infants born weighing < 1500 g [5]. It is generally accepted that a disturbance of the normal gut microbiota is a contributing factor to the development of NEC [8, 11, 12], with various associated dysbioses including reduced microbial diversity [13, 14], Plummer et al BMC Microbiology (2018) 18:184 delayed colonization of commensals including Bifidobacterium, Bacteroidetes, and Firmicutes (including Negativicutes and Clostridia), and increased abundance of Gammaproteobacteria (with reports of increased Enterobacteriaceae, Klebsiella and Escherichia/Shigella in NEC infants compared to healthy controls) [13, 15,16,17]
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