NEC has been identified as one of the most common causes of death in preterm babies at 26 to 28 gestational weeks. As a result, most of the studies that have focused on the pathogenesis of NEC have studied extremely preterm babies. In contrast with the findings in developed countries, in developing countries, such as China, only 10% of babies that are born before 28 weeks survive. However, the survival rate of infants that are born at this stage is more than 90% in developed countries. Thus, the survival gap between countries is 10: 90. Most patients with NEC in developing countries are born over 28 weeks. This study explored the constitution and function of the microbiota in patients with NEC over 28 weeks in China to provide the possible pathogenic factors.
In this study, our data were to some extent consistent with previous studies that identified no difference in the overall richness between patients with NEC (at 26–28 gestational weeks) and control infants.[7,9] However, at the phylum level, no changes were found in the Proteobacteria, Bacteroidetes, or Firmicutes between patients with NEC over 28 gestational weeks and the control group. This finding is different to those of previous studies.[7,9,11,19] This may be because the gut is well colonized in infants approaching 33 to 36 gestational weeks (the median gestational age was 34.8 for infants with NEC) in our study. Thus, the regular pattern for bacteria colonization in extremely premature babies may not apply to those babies at risk of NEC with a gestational age of over 28 weeks.
Meanwhile, it is not a surprise that we identified an increase in the abundance of Lactobacillus in the control group. Lactobacillus has been widely accepted to be a kind of probiotic. Many randomized clinic trials have demonstrated that Lactobacillus has a preventative action in NEC.[27–29] The mechanism though which Lactobacillus prevents NEC appears to involved the attenuation of interleukin (IL)-1β-induced IL-8 and IL-6 expression, decreased toll-like receptor (TLR)2, TLR4, and TLR9 expression, increased levels of specific negative regulators of inflammation (such as Single Ig IL-1-related receptor and Toll interacting protein), and the restoration of the ratio of CD4(+) Foxp3(+) regulatory T cells, which can inhibit the inflammatory activity of TH17 cells.[30–33] In addition, we discovered that Propionibacteriales was more abundant in the NEC group than in the control group, while Phascolarctobacterium was more abundant in the control group than in the NEC group. Both of these the bacteria can produce propionic acid that has been reported to maintain the intestinal immune homeostasis.[34–36] However, both of these bacteria occupied less than 0.1 percent of the total bacteria in our analysis. Thus, the influence of these bacteria may be very small.
Through function inference analysis, we also identified that NEC cases showed impaired xenobiotic biodegradation and metabolism. Xenobiotics contain drugs environmental pollutants, dietary supplements, and food additives. Dysregulation of xenobiotic metabolism may contribute to some intestinal diseases, such as ulcerative colitis. Thus, this may be the reason for the increased rate of the dysregulation of xenobiotic metabolism in patients with NEC.
The authors thank the members of the Department of Neonatology, Children's hospital, Chongqing medical university, for their help analyzing the data.
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