Hospital Regimens Including Probiotics Guide the Individual Development of the Gut Microbiome of Very Low Birth Weight Infants in the First Two Weeks of Life.

ABSTRACT

BACKGROUND: It is unknown to what extent the microbiome of preterm infants is influenced by hospital regimens including the use of different probiotics when it comes to the prevention of necrotizing enterocolitis (NEC). METHODS: Prospective controlled multicenter cohort study including very low birth weight infants from three neonatal intensive care units (NICUs) between October 2015 and March 2017. During this time span, stool was sampled every other day during the first two weeks and samples were subjected to amplicon-based microbiome analyses. Out of these, seventeen negative controls were processed (German Registry of Clinical Trials (No. DRKS00009290)). RESULTS: The groups (3 × 18 infants) showed no statistically significant difference regarding gestational age, birth weight, APGAR scores and oxygen demand. 2029 different taxa were detected, including Enterococcus and Staphylococcus, as well as the probiotic genera Lactobacillus and Bifidobacterium predominating. The bacterial load was found to increase earlier on when probiotics were used. Without probiotics administration, Lactobacillus and Bifidobacterium contributed only marginally to the fecal microbiome. Some infants did not respond to probiotic administration. The samples from all centers participating reached a very similar diversity after two weeks while the microbiome samples from all three centers clustered significantly yet varied from each other. CONCLUSION: Probiotics proved to be safe and initiated an earlier increase of bacterial load (with marked individual divergences), which might play a crucial role in the prevention of neonatal morbidities. Meconium was found not to be free of bacterial DNA, and oral antibiotics did not influence the fecal microbiome development negatively, and hospital regimes led to a center-specific, distinct cluster formation.