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

Abstract

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.

Connection between gut microbiome and brain development in preterm infants

“…Our early study demonstrated that the intestinal microbiome samples from preterm infants up through 5 weeks of life cluster distinctly from those of a full‐term breastfed infant and that the microbial patterns converge toward those of full‐term breastfed infants only at or after 6 weeks of life (Claud et al, ). We and others further demonstrated that the microbiome of the preterm infant is characterized by low diversity and high interindividual variation (Claud et al, ; Dahl et al, ; Kurokawa et al, ; Moles et al, ) with succession of bacterial classes from Bacilli to Gammaproteobacteria to Clostridia (Itani et al, ; Korpela et al, ; La Rosa et al, ; Underwood & Sohn, ). Postmenstrual age (PMA), which is the gestational age (GA) plus age of life, has been reported as the major driver in the development of the microbiome for preterm infants specifically for the rate of the assembly, with the slowest rate found in the most premature of infants (between 25 and 30 weeks of PMA; Korpela et al, ; La Rosa et al, ).…”

“…Postmenstrual age (PMA), which is the gestational age (GA) plus age of life, has been reported as the major driver in the development of the microbiome for preterm infants specifically for the rate of the assembly, with the slowest rate found in the most premature of infants (between 25 and 30 weeks of PMA; Korpela et al, 2018;La Rosa et al, 2014). A recent study corroborated this finding, demonstrating that GA is the dominant factor in microbiome assembly, independent of confounders such as mode of delivery, breastfeeding duration, and antibiotic exposure with preterm infant microbiota demonstrating lower diversity and more Proteobacteria and Enterococcus compared with full-term infants at 10 days postpartum (Dahl et al, 2018). However, the difference between preterm and term infants in bacteria diversity was not observed at 4 or 12 months postpartum, consistent with our study observing a shift of preterm microbiome to full-term infant microbiome patterns at 6 weeks of age and later (Claud et al, 2013) and confirming an age-dependent maturation of the preterm infant microbiome.…”

“…Furthermore, low levels of Bacteroides and Bifidobacterium were equally observed in both C‐section and vaginally delivered neonates in disagreement with early studies (Chu et al, ; Yassour et al, ). For preterm infants, several studies have reported that the mode of delivery does not influence the bacteria diversity difference between preterm and term infants (Dahl et al, ; Hill et al, ). Furthermore, a more recent study of preterm infant gut microbiome supported the previously mentioned studies that only GA at birth but not antibiotic exposure in the first few days of life nor mode of delivery significantly impact the bacterial alpha‐diversity among preterm infants (Chernikova et al, ).…”

“…Whether the infants are breastfed or formula‐fed also affects the microbiome in the gut (O'Sullivan, Farver, & Smilowitz, ). However, current studies do not allow us to fully assess the impact of own mother's milk feeding to preterm infants on early microbiome assembly due to the low numbers of preterm infants exclusively breastfed and the various timings that formula feeding are introduced or added (Dahl et al, ). Therefore, data on the effect of breastmilk versus formula on microbiome development are largely from studies in term infants.…”

Effects of early life NICU stress on the developing gut microbiome

“…Dobbler et al () identified low microbial diversity and chaotic succession for infants who developed NEC. The Norwegian Microbiota Study reported duration of NICU care to be a significant mediator of diversity, but not breastfeeding or history of antibiotic use (Dahl et al, ). After adjusting for antibiotic and breastmilk exposure and delivery mode, Chernikova et al () found differences in diversity based upon birth gestational age, with extremely preterm infants having less diversity than moderate–late preterm infants (Chernikova et al, ).…”