Intestinal Microbiota in the Pathogenesis and Management of Necrotizing Enterocolitis in Preterm Infants

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About this Research Topic

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Background

The pathogenesis of necrotizing enterocolitis (NEC) has been recently found to be associated with microbial dysbiosis, formula feeding, and excessive inflammation. Compared to that of term infants, the intestinal microbiota of preterm infants has fewer bacterial species, less diversity, and increased proportion of potential pathogens. The recent report of the association between early use of antibiotics and lower incidence of NEC also supports the hypothesis that microbial dysbiosis may play an important role in the development of NEC.

The microbial dysbiosis is also associated with immune dysregulation in the pathogenesis of NEC, including excessive toll-like receptor 4 (TLR4) signaling and an exaggerated inflammatory response. Previously reported microbiome studies on NEC in preterm infants may have been underpowered, but technological advances and the availability of new molecular and analytic techniques have provided greater resolution in the evaluation of neonatal intestinal microbiome. The development of microbiome in preterm infants is influenced by environmental pressure, such as antibiotic stress, instrumentation, and neonatal intensive care unit (NICU) condition. The microbial balance should be optimized to minimize pathogens and enhance beneficial organisms. It is the foundation for restoring a healthy microbial community for NEC, and should be the main therapeutic focus. Yet to date, it has not been fully investigated.

In this Research Topic, we aim to provide an overview of the most recent progress in all the areas related to intestinal microbiota in the pathogenesis and management of NEC among preterm infants, and we welcome submissions of Original Research, Review and Mini Review especially on the points below:

- Composition of the undisturbed, healthy neonatal microbiome, and the development of microbiome in preterm infants, including how environmental and iatrogenic factors affect its development. First and foremost, the microbiome in preterm infants varies over time and among patients. Follow-up of long term health consequences of the developing microbiome is important.

- Metagenomic analysis from whole genome shotgun sequencing and metabolomics that reveals the differences in the functionality of the microbiome in patients who develop NEC.

- The exact role of pathogenic bacterial strains in health and disease. Without knowing the exact mechanisms of bacterial strains in NEC, fecal microbiota transplantation (FMT) from neonatal samples may put the recipients at risk for developing the disease.

- Although multiple reports have found that there is a decreased incidence of NEC with the use of probiotics in the neonatal population, the use of probiotics is still controversial. Development of microbial therapeutic agents with pharmaceutical grade production should be further studied for preterm infants.

- Composition of an optimal microbiome for preterm infants for a stable and well-defined ecosystem.

- Immune responses of the intestinal mucosal barrier to FMT or MET in NEC should be explored. FMT is effective in modulating oxidative conditions, altering the level of representative bacteria and immune responses. Further studies focusing on immune responses including metagenomics, transcriptomics, and additional data on inflammatory mediators are needed before a broad recommendation of NEC use is made for preterm infants.

Keywords: Inflammatory response, surgical management, necrotizing enterocolitis (NEC), microbiome

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