A systematic review of associations between gut microbiota composition and growth failure in preterm neonates

ABSTRACT

Growth failure is among the most prevalent and devastating consequences of prematurity. Up to half of all extremely preterm neonates struggle to grow despite modern nutrition practices. Although elegant preclinical models suggest causal roles for the gut microbiome, these insights have not yet translated into biomarkers that identify at-risk neonates or therapies that prevent or treat growth failure. This systematic review aims to identify features of the neonatal gut microbiota that are positively or negatively associated with early postnatal growth. We identified 860 articles, of which 14 were eligible for inclusion. No two studies used the same definitions of growth, ages at stool collection, and statistical methods linking microbiota to metadata. In all, 58 different taxa were associated with growth, with little consensus among studies. Two or more studies reported positive associations with Enterobacteriaceae, Bacteroides, Bifidobacterium, Enterococcus, and Veillonella, and negative associations with Citrobacter, Klebsiella, and Staphylococcus. Streptococcus was positively associated with growth in five studies and negatively associated with growth in three studies. To gain insight into how the various definitions of growth could impact results, we performed an exploratory secondary analysis of 245 longitudinally sampled preterm infant stools, linking microbiota composition to multiple clinically relevant definitions of neonatal growth. Within this cohort, every definition of growth was associated with a different combination of microbiota features. Together, these results suggest that the lack of consensus in defining neonatal growth may limit our capacity to detect consistent, meaningful clinical associations that could be leveraged into improved care for preterm neonates.

KEYWORDS:

• Growth failure
• gut microbiome
• malnutrition
• neonate
• postnatal growth
• preterm infant
• underweight

Acknowledgments

We are grateful to Steven Ford, M.D. and Ruth Ann Luna, Ph.D. for their contributions to the original study that provided the microbiota sequencing data for our secondary analysis.

Disclosure statement

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

Data availability statement

All data and concepts described arise from the analysis of the literature detailed above (DOI: 10.1093/ajcn/nqz006).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2190301

Additional information

Funding

This project was supported by the U.S. National Institute of Diabetes and Digestive and Kidney Diseases grant/award K08 DK113114 to G.A.P., the U.S. Public Health Service grant/award P30 DK056338 which funds the Texas Medical Center Digestive Diseases Center, the Maternal and Child Health Nutrition Training Grant T79 MC00023 and the National Institute of Health (NIH) grant R01 DK124614 to A.B.H., the U.S. National Institute of General Medical Sciences T32 GM136554 training grant to L.L.N., and the Men of Distinction grant/award to A.B.H. and G.A.P.