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Distinct Gut Microbe Dynamics Detected Amongst Premature Infants with Necrotizing Enterocolitis

NEW YORK (GenomeWeb) – The microbial culprits contributing to necrotizing enterocolitis in premature infants may differ somewhat depending on when the inflammatory disease appears, according to a microbiome study appearing online last night in PLOS One.

A team from Brigham and Women's Hospital, Harvard Medical School, and elsewhere used 16S ribosomal RNA gene sequencing to follow gut microbial community patterns in a dozen infants with necrotizing enterocolitis and more than twice as many unaffected age-matched controls from the same region.

The data revealed distinct microbial community clusters in infants diagnosed with the disease in their first few weeks of life compared to those who developed necrotizing enterocolitis later on.

From these and other findings, investigators argued that there probably isn't just one main pathogen at play in necrotizing enterocolitis cases.

Instead, senior author Katherine Gregory, a newborn medicine and nursing researcher affiliated with Brigham and Women's Hospital and Harvard Medical School, and her colleagues noted that "the specific infectious agent associated with [necrotizing enterocolitis] may vary by the age of infant at disease onset."

Prior research has pointed to altered microbial colonization patterns in the guts of premature infants who develop necrotizing enterocolitis, an inflammatory bowel disease implicated in infant deaths and diminished growth and/or neurodevelopment.

Because premature birth and gut bacteria are the only risk factors reliably linked to the disease so far, Gregory and her colleagues reasoned that "when prematurity cannot be prevented, intestinal colonization is the major modifiable risk factor contributing to [necrotizing enterocolitis]."

To get at a more complete understanding of gut microbial dynamics in the days leading up to infants' diagnosis with the inflammatory disease, the researchers did 16S rRNA sequencing with the Roche 454 Titanium platform to assess 312 fecal samples from 12 infants with necrotizing enterocolitis and 26 without.

Babies in the study were born at an average gestational age of just under 28 weeks. The team collected around seven stool samples from each infant over the course of several weeks.

Using this data, the researchers tracked the dynamics of typical gut microbe colonization, contrasting it with patterns in infants diagnosed with necrotizing enterocolitis.

Microbes from the Proteobacteria, Firmicutes, and Actinobacteria phyla were common across the samples as a whole, for example. But collections of microbes found together in the gut also shifted over time as each infant's gut microbiome developed, the team noted.

When they focused on differences found in infants with or without necrotizing enterocolitis, the researchers found disease-associated gut microbe clusters that differed depending on when necrotizing enterocolitis appeared.

Infants diagnosed with necrotizing enterocolitis during the 10 to 22 days after their birth tended to carry more gut bugs from the Clostridia class at the time of diagnosis. On the other hand, those diagnosed at between 23 and 35 days after birth appeared to have higher-than-usual levels of Gammaproteobacteria microbes such as Pseudomonas, Pasteurella, Serratia, and Klebsiella.

The team also saw distinct microbe patterns in the days leading up to disease. Levels of Clostridium sensu stricto climbed prior to disease in infants with early-onset disease, while representation by Staphylococcus and other bacilli waned.

In the late onset group, though, Escherichia and Shigella bugs became prominent prior to diagnosis, but dipped closer to disease onset, when other bugs from the Gammaproteobacteria class gained abundance in the gut.

Those involved in the study cautioned that further research is needed to understand other factors influencing gut microbial patterns in the premature infant gut, including diet, mode of birth, and potential antibiotic exposures.

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