Intestinal microbiota development and gestational age in preterm neonates

Katri Korpela,Britt Nakstad,Willem De Vos,Arild E Rønnestad,Per O Iversen,Kristin Brække,Kenneth Strømmen,Sissel J Moltu,Christian A Drevon,Elin W Blakstad

doi:10.1038/s41598-018-20827-x

Abstract

The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weight < 1500 g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the first weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary effects and birth mode had little influence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and finally Bifidobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.

Highlights

Prematurity is a risk factor for infant morbidity and mortality[1], and is associated with a high risk of bacterial and inflammatory diseases, such as sepsis and necrotizing enterocolitis (NEC)
We followed the development of the intestinal microbiota longitudinally in a cohort of 45 prematurely born infants from birth to discharge from hospital up to 60 days after birth
Our results show that the promotion of normal microbiota development in prematurely born infants is possible in a hospital setting, because many infants progressed to a Bifidobacterium-dominated composition which is characteristic of healthy term-born non-hospitalized infants

Summary

Introduction

Prematurity is a risk factor for infant morbidity and mortality[1], and is associated with a high risk of bacterial and inflammatory diseases, such as sepsis and necrotizing enterocolitis (NEC). Studies with small groups of infants have indicated that both NEC and late-onset sepsis are associated with alterations in the microbiota[8,9,10,11], and that the microbiota composition correlates with signs of pain and distress[17]. Promoting a healthy microbiota development in preterm infants is important, and a key question is whether natural colonization and succession of the microbiota is possible in these infants. Studies on the preterm microbiota have been conducted[4,5,6,7,8,9,10,11], they involve only a handful of infants and none show detailed microbiota succession. To establish a defined and predictive picture of the preterm infant microbiota development, we analyzed 262 fecal samples from 45 preterm infants using deep 16S rRNA amplicon sequencing

Methods

Results

Conclusion