Preterm infants have distinct microbiomes not explained by mode of delivery, breastfeeding duration or antibiotic exposure

Background: Preterm infants have low gut microbial diversity and few anaerobes. It is unclear whether the low diversity pertains to prematurity itself or is due to differences in delivery mode, feeding mode or exposure to antibiotics. Methods: The Norwegian Microbiota Study (NoMIC) was established to examine the colonization of the infant gut and health outcomes. 16S rRNA gene Illumina ampliconsequenced samples from 519 children (160 preterms), collected at 10 days, 4 months and 1 year postnatally, were used to calculate alpha diversity. Short-chain fatty acids (SCFA) were analysed with gas chromatography and quantified using flame ionization detection. We regressed alpha diversity on gestational age, taking into account possible confounding and mediating factors, such as breastfeeding and antibiotics. Taxonomic differences were tested using Analysis of Composition of Microbiomes (ANCOM) and SCFA profile (as a functional indicator of the microbiota) was tested by Wilcoxon rank-sum. Results: Preterm infants had 0.45 Shannon units lower bacterial diversity at 10 days postnatally compared with infants born at term (95% confidence interval: -0.60, -0.32). Breastfeeding status and antibiotic exposure were not significant mediators of the gestational age-diversity association, although time spent in the neonatal intensive care unit was. Vaginally born, exclusively breastfed preterm infantss not exposed to antibiotics at 10 days postnatally had fewer Firmicutes and more Proteobacteria than children born at term and an SCFA profile indicating lower saccharolytic fermentation. Conclusions: Preterm infants had distinct gut microbiome composition and function in the early postnatal period, not explained by factors more common in preterms, such as shorter breastfeeding duration, more antibiotics or caesarean delivery.