Abstract
Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention.
Highlights
Postnatal growth failure is a pervasive problem among preterm infants that occurs during a critical developmental period
We found that extremely preterm (EPT) infants with postnatal growth failure had disrupted maturation of the microbiota characterized by low diversity, persistent dominance of Enterobacteriaceae, and a paucity of strictly anaerobic taxa including Veillonella compared to infants with appropriate growth
The infants with growth failure demonstrated a metabolic signature of increased lipolysis and fatty acid oxidation, characterized by elevations in multiple fatty acids, acylcarnitines, glycerol, and β-hydroxybutyric acid
Summary
Postnatal growth failure is a pervasive problem among preterm infants that occurs during a critical developmental period. Poor growth in the NICU is a risk factor for poor neurodevelopmental outcomes, including cognitive and motor impairment, and the metabolic adaptations associated with early life growth failure may predispose preterm infants to obesity and other adverse cardiometabolic outcomes in later life[4,5,6]. There are a number of potential mechanisms by which the altered microbiota and the bioactive metabolites produced by microbial metabolism may affect growth and metabolism in preterm infants, including direct effects on nutrient acquisition and utilization as well as indirect effects on intestinal development, inflammation, and hormonal signaling[18,19,20,21]. To investigate the relationships between the intestinal microbiota, host metabolism, and growth, we conducted a longitudinal, prospective cohort study of EPT infants throughout their NICU hospitalization. We hypothesized that the diagnosis of severe postnatal growth failure would be preceded by perturbations in the development of the microbiota and host metabolome
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