Early gut microbiota in very low and extremely low birth weight preterm infants with feeding intolerance: a prospective case-control study

The potential role of the gut microbiota in the pathogenesis of feeding intolerance (FI) remains unclear. Understanding the role of the gut microbiota could provide a new avenue for microbiota-targeted therapeutics. This study aimed to explore the associations between aberrant gut microbiota and FI in very low or extremely low birth weight (VLBW/ELBW) preterm infants. In this observational case-control study, VLBW/ELBW infants were divided into two groups: FI group and feeding tolerance (FT) group. 16S rRNA gene sequencing was performed to analyze the gut microbial diversity and composition of the infants. The differences in the gut microbiota of the two groups were compared. In total, 165 stool samples were obtained from 44 infants, among which, 31 developed FI and 13 served as controls. Alpha diversity was the highest in the meconium samples of the two groups. LEfSe analysis revealed that the abundances of Peptostreptococcaceae, Clostridiales and Clostridia in the FT group were significantly higher than in the FI group. At the phylum level, the FI group was dominated by Proteobacteria, and the FT group was dominated by Firmicutes. The meconium samples of the FI group had higher proportions of γ-proteobacteria and Escherichia-Shigella and a lower proportion of Bacteroides compared with the FT group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that aberrant gut bacteria in the FI group were strongly associated with dysregulation of C5-Branched-dibasic-acid-metabolism, protein kinases, and sporulation. These findings reveal candidate microbial markers to prevent FI. Increased relative abundances of γ-proteobacteria and Escherichia-Shigella and decreased abundance of Bacteroides in meconium were associated with an increased risk of FI, while Peptostreptococcaceae, Clostridiales and Clostridia reduced the risk of FI in VLBW/ELBW infants.