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Team IDs Potential Gut Microbe Marker for Necrotizing Enterocolitis in Infants

NEW YORK (GenomeWeb) – The presence of certain Escherichia coli strains in the gut may serve as a markers for necrotizing enterocolitis risk in preterm infants, according to a study appearing online today in Cell Reports.

Researchers from the US and Italy did metagenomic sequencing on DNA in stool samples from 144 preterm infants and nearly two dozen more full-term infants, using the sequences to profile microbial gene repertoires and to do multi-locus sequence type (MLST) analyses of microbial community members in the infants' guts.

When it compared the genes and organisms found in infants with and without necrotizing enterocolitis, the team saw several E. coli strains that tended to coincide with necrotizing enterocolitis — namely uropathogenic E. coli (UPEC) strains previously implicated in urinary tract infections.

"Our study suggests that if you can quickly identify UPEC in the microbiome of a pre-term infant, you can know that the infant has a greater risk for NEC before there are any symptoms," co-first author Doyle Ward, a microbiologist with the University of Massachusetts Medical School's Center for Microbiome Research, said in a statement. "[I]f we can identify these organisms early enough in a pre-term infant, and learn about them in advance, we can arm physicians with information that could help them make care decisions for these vulnerable infants."

Necrotizing enterocolitis affects almost one-tenth of infants born before 32 weeks, and causes intestinal tissue damage, necrosis, diarrhea, and other symptoms that prove fatal in almost one-third of affected infants. Although past studies suggest gut microbiomes tend to shift to contain higher-than-usual levels of Enterobacteriaceae family microbes when necrotizing enterocolitis occurs, this dysbiosis is not specific to such infections and often occurs in preterm infants without the condition.

To get a closer look at gut microbes that might contribute to necrotizing enterocolitis, the researchers assessed stool samples from 144 preterm infants in three neonatal intensive care units at hospitals in Cincinnati and Birmingham who'd been born before 30 weeks, as well as samples from 22 infants born after 37 weeks. They used metagenomic sequencing to assess gene sequences and species present in samples from between 3 days and 22 days after birth, comparing patterns in the 27 preterm infants who developed necrotizing enterocolitis with those present in infants who did not. To account for shifts in the gut microbiome during development, samples collected over three different weeklong windows after birth were first analyzed separately.

In samples available during the first week, the team found higher gut microbial diversity in the full-term infants, who tended to show enrichment for Actinobacteria, Bacteroidetes, and Firmicutes bacteria. In contrast, the preterm gut microbiomes were much less diverse and tended to include distinct types of bacteria from some of the same phyla. Similar differences between term and preterm infant gut microbes turned up at subsequent time points, as did diversity dips associated with antibiotic use.

When they looked more closely at the microbes associated with deadly necrotizing enterocolitis cases, however, the researchers were struck by the presence of E. coli enrichment in stool samples from 10 of the 15 preterm infants who died from the condition. Klebsiella species dominated in gut microbiomes for a dozen preterm infants with necrotizing enterocolitis, including four who died, and both E. coli and Klebsiella species turned up in the gut microbiomes of the two remaining necrotizing enterocolitis cases.

The team's subsequent gene-based and MLST analyses suggested that the relationship between E. coli and severe necrotizing enterocolitis may not be universal. Instead, the accessory genes and sequence types found in strains that clustered with infection cases indicated that UPEC strains such as ST127, ST144, ST131 may be particularly prominent in infants with serious and sometimes deadly necrotizing enterocolitis.