Preterm infant weight gain patterns are not associated with gut microbiome measures

Among very low birth weight (VLBW; <1500g) infants, failure to gain appropriate weight during hospitalization is associated with adverse outcomes. The gut microbiome contributes to nutrient accretion. Perturbation of the assembly of intestinal microbial communities in term infants has been linked to growth failure. However, if the microbiome modulates growth in preterm infants, and particularly growth faltering, a potentially more clinically relevant marker of malnutrition in preterm infants has not been explored.Prospective cohort study of 101 VLBW infants with 855 serial fecal specimens collected from birth to hospital discharge and sequenced using shotgun metagenomics. The stool microbiome was evaluated in infants with growth faltering categorized as a reduction in weight-for-age z scores from birth to 36 weeks PMA: <=0.8 (none), >0.8 to 1.2 (mild); >1.2 (moderate to severe), and in infants with growth failure (<3rd percentile weight-for-age) at 36 weeks PMA. In a subset of 46 infants and 202 samples, fecal metabolomics was performed using 1H NMR-based metabolomics. All analyses were adjusted for postnatal age and birthweight z-score, and additionally with variables for diet and antibiotic exposure as appropriate.At 36 weeks PMA, 18% of infants had growth failure, and 53.5% had growth faltering. Both definitions identified distinct populations of infants. Age was associated with significant changes in microbiome composition, gene abundance, and metabolite concentration. When adjusting for postnatal age, infants in the comparator groups did not differ in diversity or taxonomic composition. Microbial genomic composition analysis of the 500 most abundant Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs (KO) showed that 3 KOs were decreased in mild growth faltering; 1 KO was decreased, and 5 KOs were increased in moderate to severe faltering. The glycolysis and gluconeogenesis pathway was decreased in abundance among infants with moderate to severe faltering. No differences in the top 500 KO were found in infants with and without growth failure. Metabolite concentrations were not significantly different in the study groups. Microbiome maturity models identified a lag in maturity among infants with growth failure, but not in infants with growth faltering.In contrast to older children with deprivation-related malnutrition, there were minimal differences in microbiome measures in preterm infants with growth faltering or growth failure, except for a delay in microbiome maturity among infants with growth failure.