Preterm infants with two types of dysbiosis, or an imbalance of gut microbiota, are more likely to develop necrotizing enterocolitis, and within distinct time frames, based on the results of a small prospective cohort study.
Necrotizing enterocolitis (NEC) is an intestinal disorder that affects 10% of infants born before the 29th week and is fatal in about 30% of those affected. It has long been thought to be related to intestinal colonization, as preterm infants are known to have fewer beneficial organisms, lower bacterial diversity, and more pathogens, than healthy term infants. However, a clear understanding of the pathogenesis of NEC and the timing of its onset has thus far eluded investigators.
For their research, epidemiologist Ardythe L. Morrow, Ph.D., of Cincinnati Children’s Hospital Medical Center, and colleagues, examined the early microbial community of 11 preterm infants who later developed NEC and that of 21 controls matched for gestational age, birth weight, and other factors who did not develop NEC. The researchers used gene sequencing of stool samples taken between 4 and 16 days after birth to identify microbial community signatures, and urine samples to identify bacteria-derived metabolites of NEC (Microbiome 2013 [doi:10.1186/2049-2618-1-13]).
Infants whose microbial communities were dominated by gram-positive Firmicutes (class Bacilli, with the dominant genera Staphylococcus and Enterococcus) between 4 and 9 days of life had a significantly higher risk of developing NEC by 21 days compared with matched controls, Dr. Morrow and colleagues found. Infants with evidence of gram-negative Proteobacteria (Enterobacteriaceae, with the dominant genera Enterobacter and Escherichia) at 10-16 days had an increased risk of developing NEC later – between 19 and 39 days of life – compared with controls.
The absence of Propionibacterium organisms in stool samples taken in the first week after birth was associated with a significantly higher risk of developing NEC, and this factor combined with evidence of dysbiosis in the first 2 weeks of life was highly predictive of NEC. A high urinary alanine to histidine ratio also was highly predictive of NEC (82% of infants with NEC vs. 25% of controls). Propionibacterium occurred in more than half of the healthy controls and none of the infants who went on to develop NEC.
Dr. Morrow and colleagues’ study is the first to identify the role and timing of early gram-positive and gram-negative forms of dysbiosis in the development of NEC. It also underscored the potential beneficial role of Propionibacterium in the intestinal health of preterm infants.
The study was funded by grants from the National Institutes of Health and the Department of Health and Human Services. None of the authors disclosed relevant financial conflicts.