Temporal dynamics of the gut microbiome and metabolome in preterm and term infants from birth through the first year of life

Abstract Background: Emerging evidence has shown a link between the perturbations and development of the gut microbiota in infants to their immediate and long-term health. In comparison to the healthy full-term neonate, preterm neonates experience disparate gut bacterial establishment (e.g. duration in the womb), colonisation (e.g. mode of delivery), and development (e.g. frequent use of antibiotics). To better understand the assembly of the gut microbiota in preterm infants, faecal samples were longitudinally collected from preterm (n = 19) and term (n = 20) infants, up to 12 months after birth. We characterised bacterial compositions by 16S rRNA gene sequencing (n = 141) and metabolomics profiling (n = 141) using nuclear magnetic resonance (NMR) spectroscopy.Results: Significant differences in faecal bacterial composition between term and preterm infants were detected in sample collected in week 2, month 6 and month 12. Interestingly, separation of the bacterial composition between term and preterm infants was more pronounced at month 12 as compared to the earlier time-points, suggesting distinct level of microbial maturation in gut between the two groups. Intestinal microbiota of preterm neonates was consistently characterised by dominance of pathogenic bacteria from the Enterobacteriaceae family and a paucity of strictly anaerobic taxa including Veillonella and Bacteroides relative to infants born at term. Consistent result was observed in the stool NMR spectroscopy in which clear separation in stool metabolomics profiles was observed between the term and preterm neonates.Conclusion: Overall, we identified a panel of amino acid metabolites and central metabolism intermediates in the preterm infants’ stool, possibly indicating incomplete fermentation of complex polysaccharides in the guts of these infants. In contrast, the term infant stool had significantly higher levels of metabolites which are commonly found in milk such as fucose and β-hydroxybutyrate (BHBA). Birth weight was selected as the best explanatory variable for the metabolomics profiles, pointing to the strong relationship between protein synthesis, as well as fucose and BHBA in physical development. By following both term and preterm infants for 12 months, our study reported the dynamic of gut microbial composition and their contribution to metabolism and potential impact to growth in neonates.