Preterm birth affects the gut microbiota, metabolome and health outcomes of twins at 12 months of age: a case control study

Abstract

Perinatal factors can influence gut microbiota, adversely impacting infant health outcomes. However, little is known about the combined effect of preterm birth and chorionicity on gut microbiota, metabolism, physical and neurobehavioral development for twin infants. In this study, we profiled and compared the gut microbial colonization of 350 twins aged 12 months. Twins were divided into four groups based on their gestational age at birth and chorionicity as dichorionic-diamniotic full-term birth group, dichorionic-diamniotic preterm-birth group, monochorionic-diamniotic full-term birth group, and monochorionic-diamniotic preterm birth group. Gut microbiota diversity and fecal metabolic alterations at 12 months old were determined by 16S rDNA sequencing and untargeted metabolomics, respectively. Wilcoxon's rank-sum tests were used to compare alpha diversity between the four groups. The general linear models were applied to identify microbiota species that were differentially abundant among the four groups and the health effects of gut microbiota on physical and neurobehavioral development conducted at 12 months of age. In addition, the twin-based ACE model was used to evaluate the contribution of genetic and environmental effects on the composition and function of the gut microbiota. We found that preterm birth and chorionicity dominated genetics in altering the composition of gut microbiota and concentration of metabolites over 12 months of age. The influence of genetic factors differed between preterm and full-term births. There were 16 gestational age and chorionicity specified gut microbiota genera and 285 group-specified metabolites. Association analysis filtered 7 microbiota genera and 19 metabolites associated with twins' physical and neurobehavioral development. Three metabolites, N-Oleoyl dopamine, Ecgonine, and Methyl jasmonate participated in the neuroactive ligand-receptor interaction pathway, tropane, piperidine, and pyridine alkaloid biosynthesis pathway, and alpha-Linolenic acid metabolism and biosynthesis of secondary metabolites, respectively. We concluded that preterm birth is associated with dysbiotic microbiota profiles and significant metabolic alterations, which may eventually influence physical and neurobehavioral development.