Probiotics and necrotizing enterocolitis

Abstract

In this review, we summarize existing knowledge regarding the effects of probiotics on necrotizing enterocolitis (NEC). We review the role of the microbiome in NEC and pre-clinical data on mechanisms of probiotic action. Next, we summarize existing randomized controlled trials and observational studies of probiotics to prevent NEC. We also summarize findings from several recent meta-analyses and report a new cumulative meta-analysis of probiotic trials. Finally, we review data from cohorts routinely using commercially available probiotics. Our goal is to inform clinicians about the risks and benefits of probiotics, which may be helpful for those considering use in preterm infants to prevent NEC, death, or sepsis.

Keywords: Bacteria; Gut; Meta-analysis; Microbiome; Neonate; Preterm.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1. Mechanisms of probiotic action

Figure depicts potential mechanisms by which probiotics exert beneficial effects on the immature gut. Abbreviations: TLR-4, Tolllike receptor 4, TJ, tight junction; NFΚB, nuclear factor kappa B.

Figure 2. Cumulative pooled meta-analysis of the effects of probiotics on NEC

The cumulative pooled risk ratio for NEC among trials from 1997 through 2016. Studies selected from a recent meta-analysis (DOI: 10.7717/peerj.2429/supp-1)(35) and sorted, first, by year of publication and then alphabetically by author. Cumulative pooled risk ratios (Mantel-Haenszel method with random effects model) including each study along with prior studies generated using RevMan 5.3 (Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). The N reflects the cumulative number of enrolled patients. Abbreviations: NEC, necrotizing enterocolitis; N/A, no applicable as no events in either group; N, cumulative number of infants; RR, relative risk; CI, confidence interval.

Figure 3. Treatment effects of probiotics in randomized trials and observational studies

Pooled risk ratios with error bars to indicate 95% CI (Mantel-Haenszel method with fixed effects) are reported along with sample sizes for each pooled estimate with corresponding statistical measure of heterogeneity (I2). Data from Dermyshi E. et al. The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants. Neonatology. 2017 (39). Abbreviations: RR, relative risk; CI, confidence interval; NEC, necrotizing enterocolitis; RCT, randomized controlled trials; OBS, observational studies; LOS, late-onset sepsis.