Necrotizing Enterocolitis and Changes in Gut Bacteria: Which Is the Chicken and Which Is the Egg?

William T. Basco, Jr., MD, MS


July 28, 2016

Gut Bacteria Dysbiosis and Necrotising Enterocolitis in Very Low Birthweight Infants: A Prospective Case-Control Study

Warner BB, Deych E, Zhou Y, et al
Lancet. 2016;387:1928-1936

Stool Microbiota and Necrotizing Enterocolitis

Epidemiologic evidence demonstrates that necrotizing enterocolitis (NEC) occurs in up to 10% of very low birthweight (VLBW) infants. Previous studies have also shown that antibiotic exposure increases the risk for NEC, and studies indicate that probiotics and human breastmilk feedings can reduce the risk. For those reasons, investigators have questioned whether adverse alterations in gut bacteria are part of the causal pathway to developing NEC. This study collected data from three US medical centers to determine whether changes in stool microbiota over time are indicative of the development of NEC. The study enrolled 971 infants with a birthweight of ≤ 1500 g and serially collected stools from these infants. DNA analysis was used to identify bacterial types in each stool, and then stools from infants who developed NEC (n = 28) were compared with the stools of control infants (n = 94).

Significant differences between infants in the NEC and control groups included lower 5-minute Apgar scores, more days on antibiotics, and a greater frequency of having had a blood transfusion in the NEC group. Infants in the NEC group also weighed less at birth and were more likely to be black (79% of cases vs 48% of controls). Three classes of bacteria—bacilli, Gammaproteobacteria, and the obligate anaerobes Clostridium and Negativicutes—constituted more than 90% of stool isolates. In general, the stool samples of the children who did not develop NEC continued to gain microbiota diversity as the infants aged, whereas the stools of infants who developed NEC had higher proportions of Gammaproteobacteria (facultative gram-negative organisms) and lower proportions of the anaerobic bacteria, Clostridium and Negativicutes. Bifidobacteria were not very common, comprising less than 3% of the stool bacteria. The authors concluded that the underrepresentation of obligate anaerobic bacteria such as Clostridium and Negativicutes support the idea that dysbiosis precedes NEC.


The microbiome research that is going on right now, involving many different disease processes, is really fascinating. Not all of the disease processes currently hypothesized to be caused or modified by gut bacteria will, in the end, be confirmed as being related to changes in gut bacteria. Still, I am excited by the idea that we may be able to use gut flora as markers for future disease in a predictive or diagnostic sense as well as a way to monitor the effectiveness of therapy. It may even be the case that microbiome therapy will become a mainstay of treatment for some diseases. In an editorial/summary of the research paper in JAMA,[1] the editorialist comments that it is unclear whether alteration of gut flora is part of the cause or effect in most diseases, but it will be interesting over subsequent years to see whether additional studies can produce risk-stratification levels based on microbiome patterns. Then, the question will be whether these risk strata can help us identify who might benefit most from other interventions or whether it is the improvement of the gut microbiome that will actually be therapeutic.



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