Spatiotemporal development of late and moderate preterm infant gut and oral microbiomes and impact of gestational age on early colonization

Microbiome research focusing on late and moderate preterm infants (LMPT; 32 to 36 weeks gestation) is limited, despite rising LMPT births, large healthcare burdens, and increased risks of multiple morbidities, potentially microbially related. In this longitudinal cohort study, 16S rRNA gene sequencing was used to analyze 371 stool and 402 saliva samples from 160 LMPT infants, collected at five time points between birth and 12 months corrected age (CA), to describe spatial and temporal variability in gut and oral microbiomes. Paired stool and saliva samples (<i>n</i> = 337) were analyzed for potential microbial relationships. Early LMPT samples (up to 60 days of life; DOL) were also compared with data from seven extremely preterm infants (EP; <28 weeks gestation; stool <i>n</i> = 14, saliva <i>n</i> = 14). LMPT stool and saliva were composed of distinct microbial communities at each time point, and both sample types showed increasing alpha diversity over time. Stool was initially dominated by <i>Escherichia/Shigella, Klebsiella</i>, and <i>Streptococcus</i>, with <i>Bifidobacterium</i> becoming dominant from term equivalent age (TEA). Contrarily, saliva was dominated by <i>Streptococcus</i> throughout the first year, with early contributions from <i>Staphylococcus</i> and later <i>Veillonella</i>. LMPT infants had higher stool and lower saliva diversity compared with EP infants. Both sample types from EP infants were taxonomically distinct from LMPTs, with <i>Escherichia/Shigella</i> dominating both EP sample types throughout the first 60 DOL. The results highlight the unique trajectories of LMPT microbiomes and emphasize the role of gestational maturity in shaping microbial communities.IMPORTANCEThe oral and gut microbiome develops from birth and plays important roles in health. This has been well studied in extremely preterm infants (EP; born <32 weeks gestation) and term infants (born >38 weeks gestation), but there is a paucity of research describing oral and gut microbiome development in late and moderate preterm infants (LMPT; 32 to 36 weeks gestation). Our study analyzed microbiome development in 160 LMPT infants from birth to 12 months corrected age. The results showed distinct microbial communities in stool and saliva, with increasing alpha diversity and niche specification over time. LMPT infants' gut microbiome became dominated by <i>Bifidobacterium</i> by month 3, while the oral community was consistently dominated by <i>Streptococcus</i>. These results highlight that LMPT infants have gut and oral microbiome development that is more like term infants than EP infants, which has important implications for the care of LMPT infants.