Effects of early life NICU stress on the developing gut microbiome.

Succession of gut microbial community structure for newborns is highly influenced by early life factors. Many preterm infants cared for in the NICU are exposed to parent-infant separation, stress, and pain from medical care procedures. The purpose of the study was to investigate the impact of early life stress on the trajectory of gut microbial structure. Stool samples from very preterm infants were collected weekly for 6 weeks. NICU stress exposure data were collected daily for 6 weeks. V4 region of the 16S rRNA gene was amplified by PCR and sequenced. Zero-inflated beta regression model with random effects was used to assess the impact of stress on gut microbiome trajectories. Week of sampling was significant for Escherichia, Staphylococcus, Enterococcus, Bifidobacterium, Proteus, Streptococcus, Clostridium butyricum, and Clostridium perfringens. Antibiotic usage was significant for Proteus, Citrobacter, and C. perfringens. Gender was significant for Proteus. Stress exposure occurring 1 and 2 weeks prior to sampling had a significant effect on Proteus and Veillonella. NICU stress exposure had a significant effect on Proteus and Veillonella. An overall dominance of Gammaproteobacteria was found. Findings suggest early life NICU stress may significantly influence the developing gut microbiome, which is important to NICU practice and future microbiome research.

The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota.

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.

Predicted Metabolic Pathway Distributions in Stool Bacteria in Very-Low-Birth-Weight Infants: Potential Relationships with NICU Faltered Growth.

Many very-low-birth-weight (VLBW) infants experience growth faltering in early life despite adequate nutrition. Early growth patterns can affect later neurodevelopmental and anthropometric potentials. The role of the dysbiotic gut microbiome in VLBW infant growth is unknown. Eighty-four VLBW infants were followed for six weeks after birth with weekly stool collection. DNA was extracted from samples and the V4 region of the 16S rRNA gene was sequenced with Illumina MiSeq. A similar microbiota database from full-term infants was used for comparing gut microbiome and predicted metabolic pathways. The class Gammaproteobacteria increased or remained consistent over time in VLBW infants. Out of 228 metabolic pathways that were significantly different between term and VLBW infants, 133 pathways were significantly lower in VLBW infants. Major metabolic differences in their gut microbiome included pathways involved in decreased glycan biosynthesis and metabolism, reduced biosynthetic capacity, interrupted amino acid metabolism, changes that could result in increased infection susceptibility, and many other system deficiencies. Our study reveals poor postnatal growth in a VLBW cohort who had dysbiotic gut microbiota and differences in predicted metabolic pathways compared to term infants. The gut microbiota in VLBW infants likely plays an important role in postnatal growth.

Contributors to Dysbiosis in Very-Low-Birth-Weight Infants.

The objective of this commentary was to analyze the causes and outcomes of gut microbiome dysbiosis in preterm infants who are born at very low birth weight (VLBW). The intrauterine development of VLBW infants is interrupted abruptly with preterm birth and followed by extrauterine, health-threatening conditions and sequelae. These infants develop intestinal microbial dysbiosis characterized by low diversity, an overall reduction in beneficial and/or commensal bacteria, and enrichment of opportunistic pathogens of the Gammaproteobacteria class. The origin of VLBW infant dysbiosis is not well understood and is likely the result of a combination of immaturity and medical care. We propose that these factors interact to produce inflammation in the gut, which further perpetuates dysbiosis. Understanding the sources of dysbiosis could result in interventions to reduce gut inflammation, decrease enteric pathology, and improve health outcomes for these vulnerable infants.