Gut microbiome in preterm infants with different weight gain outcomes

Inadequate in-hospital weight gain among very low birth weight (VLBW; <1500g) infants is associated with adverse outcomes. Although microbiome alterations are linked to malnutrition in older children, their association with VLBW weight gain outcomes remains unclear.

To evaluate associations between fecal microbiome composition, functional gene pathways, and metabolomic profile, and abnormal weight gain in VLBW infants.

Prospective cohort study of VLBW infants from birth to hospital discharge with weekly fecal sampling. Inadequate weight gain was defined at 36 weeks post-menstrual age, as growth faltering (decline in weight-for-age z-scores from birth) and growth failure (<3^rd percentile weight-for-age). Growth faltering was categorized as mild (0.8-1.2 decline) and moderate-severe (>1.2 decline). Fecal samples underwent shotgun metagenomic sequencing with KEGG-based functional annotation; ¹H NMR-based metabolomics was performed in a subset.

Among 101 enrolled infants, 54% had growth faltering (28 mild; 26 moderate-severe), and 18% had growth failure. The two outcomes rarely co-occurred (n=7). Microbiome diversity and taxonomic composition changed with age but did not differ by growth outcomes. Infants with moderate-to-severe faltering had reduced abundance of the glycolysis/gluconeogenesis pathway. Infants with growth failure showed a significant lag in microbiome maturity. Metabolite concentrations measured in a subset (n=46) were not significantly different in the study groups.

Abnormal weight gain in VLBW infants was not associated with major differences in microbial compositional or fecal metabolite levels. Differences identified in pathway analysis and in microbiome maturation may help focus future efforts to investigate the gut microbiome's role in VLBW weight gain.