Necrotizing enterocolitis (NEC) is an inflammatory disease of the newborn bowel, primarily affecting premature infants. Early intestinal colonization has been implicated in the pathogenesis of NEC. The objective of this prospective case-control study was to evaluate differences in the intestinal microbiota between infants who developed NEC and unaffected controls prior to disease onset. We conducted longitudinal analysis of the 16S rRNA genes of 312 samples obtained from 12 NEC cases and 26 age-matched controls with a median frequency of 7 samples per subject and median sampling interval of 3 days. We found that the microbiome undergoes dynamic development during the first two months of life with day of life being the major factor contributing to the colonization process. Depending on when the infant was diagnosed with NEC (i.e. early vs. late onset), the pattern of microbial progression was different for cases and controls. The difference in the microbiota was most overt in early onset NEC cases and controls. In proximity to NEC onset, the abundances of Clostridium sensu stricto from Clostridia class were significantly higher in early onset NEC subjects comparing to controls. In late onset NEC, Escherichia/Shigella among Gammaproteobacteria, showed an increasing pattern prior to disease onset, and was significantly higher in cases than controls six days before NEC onset. Cronobacter from Gammaproteobacteria was also significantly higher in late onset NEC cases than controls 1-3 days prior to NEC onset. Thus, the specific infectious agent associated with NEC may vary by the age of infant at disease onset. We found that intravenously administered antibiotics may have an impact on the microbial diversity present in fecal material. Longitudinal analysis at multiple time points was an important strategy utilized in this study, allowing us to appreciate the dynamics of the premature infant intestinal microbiome while approaching NEC at various points.

Background Intestinal colonization during infancy is important to short and long term health outcomes. Bacteroides, an early member of the intestinal microbiome, are necessary for breaking down complex molecules within the intestine and function to assist the body’s immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. Purpose This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants based on clinical factors including mode of birth, antibiotics, and nutrition. Methods Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real time polymerase chain reaction (PCR). Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. Results We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via Cesarean section (p<.001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. Implications for Practice These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via Cesarean section aimed at overcoming delayed Bacteroides colonization. Implications for Research Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health.