Dichotomous development of the gut microbiome in preterm infants

Abstract

BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0–90%) at ≤ 2 weeks, 69.7% (29.9–86.9%) in the 3rd, and 75.5% (54.5–86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants.Electronic supplementary materialThe online version of this article (10.1186/s40168-018-0547-8) contains supplementary material, which is available to authorized users.

Evolution of Gut Microbiome and Metabolome during Stage 1 Necrotizing Enterocolitis: a Case-Control Study

“…NEC-1 children showed a high general variance for gut microbiota and fecal metabolome which is in line with a personalized microbiota and fecal metabolome profiles of preterm infant [18]. Both this datum and the delayed intestinal colonization of preterm infants [19,20] may explain the lack of NEC-1-specific microbial group in the first decade of life. The analysis by decades of life revealed a divergence for both gut microbiota and microbiome in NEC-1 by the third decade of life.…”

Effects of early life NICU stress on the developing gut microbiome

“…This study was conducted using secondary data. VLBW infant participants were part of a larger longitudinal study of long-term growth, health, and neurodevelopmental effects (Groer, Ashmeade, Duffy, Morse, & Zaritt, 2016;Groer, Ashmeade, Louis-Jacques, Beckstead, & Ji, 2016;Ho et al, 2018). Infants were admitted to the neonatal intensive care unit at Tampa General Hospital in Tampa, Florida between 2011 and 2015.…”

Mode of delivery and weight shape the intestinal microbiome composition progression in preterm infants: results of a prospective study

“…Previous studies on the intestinal microbiome of preterm infants, using 16S rRNA-based sequencing technologies, have revealed remarkable differences with the microbiome of term infants, including higher abundances of bacilli and Gammaproteobacteria [14][15][16][17][18][19][20][21][22][23][24][25][26]. The process of microbiota maturation, a pattern where microbiome maturation is mirrored by the maturation of the infant, is important in understanding differences between the microbiome of preterm-and term infants.…”

“…Besides host biology, such as low birth weight (BW) and immaturity of the multiple organs including the gastrointestinal tract as a result of low gestational age (GA), there are multiple other exogenous factors that could affect the intestinal microbiome development/maturation of preterm infants (i.e. mode of delivery, neonatal feeding regime, the neonatal intensive care unit (NICU) environment and peri-and postnatal antibiotic exposure) [5,6,14,16,19,29].…”

“…While interest in this subject is growing, the focus of research is typically, with a few exceptions [15][16][17][18][19]23], on the relation between the intestinal microbiome of the preterm infant and disease instead of on microbiome composition development itself. We aimed to determine whether the early microbiome development in extremely premature infants born between 25 and 30 weeks of gestation is dependant by infant maturity/maturation or whether it is mainly characterized by varying states of dysbiosis.…”