Microbiome-targeting therapies in the neonatal intensive care unit: safety and efficacy

ABSTRACT

Microbiome-targeting therapies have received great attention as approaches to prevent disease in infants born preterm, but their safety and efficacy remain uncertain. Here we summarize the existing literature, focusing on recent meta-analyses and systematic reviews that evaluate the performance of probiotics, prebiotics, and/or synbiotics in clinical trials and studies, emphasizing interventions for which the primary or secondary outcomes were prevention of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and/or reduction in hospitalization length or all-cause mortality. Current evidence suggests that probiotics and prebiotics are largely safe but conclusions regarding their effectiveness in the neonatal intensive care unit have been mixed. To address this ambiguity, we evaluated publications that collectively support benefits of probiotics with moderate to high certainty evidence in a recent comprehensive network meta-analysis, highlighting limitations in these trials that make it difficult to support with confidence the routine, universal administration of probiotics to preterm infants.

KEYWORDS:

• Preterm infants
• probiotics
• prebiotics
• synbiotics
• necrotizing enterocolitis
• late-onset sepsis
• feeding intolerance
• bifidobacteria
• lactobacilli

Acknowledgments

We would like to thank David Zahrah from the Dantas Laboratory for confirming translations from Spanish language publications. P.I.T. is a holder of equity in, a member of the Scientific Advisory Board of, and a consultant to, MediBeacon Inc., which is developing technology to measure human intestinal permeability. He is also the inventor of intellectual property that could earn royalties if this technology results in a clinical product.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is supported by the National Institute of General Medical Sciences (R01 GM099538 to G. D.), the National Institute of Diabetes and Digestive and Kidney Diseases (5P30 DK052574 to P. I. T. Administrative Core), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD092414 to G. D., B. B. W., and P. I. T.), and the Children’s Discovery Institute at St Louis Children’s Hospital and Washington University School of Medicine in St Louis (B. B. W. and P. I. T.). A. D. is supported by the Cellular & Molecular Biology Training Grant (T32GM139774).