Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators
Section snippets
Necrotizing enterocolitis
Necrotizing enterocolitis (NEC) is a major cause of mortality in preterm infants who survive the first few days after birth [1,2]. NEC is seen in 7% of very low birth weight infants (birth weight <1500 g) and up to 5% of admissions to the neonatal intensive care unit (NICU) [2,3]. NEC is associated with a mortality of 15–30% and a significant long-term neurodevelopmental morbidity but we have made little progress for 60 years [[3], [4], [5]]. The pathogenesis of NEC is not clear but microbial
Microbiome and human health
The microbial communities on the surface of the human body outnumber human cells and genes. Host–microbe interactions on intestinal and respiratory mucosal surfaces play a major role in the prevention of infections and development of immunity. Intestinal microbiota, the best studied, has a bacterial load in the magnitude of 1014 bacteria/mm3, which makes it the most densely colonized surface of the human body. Bacteroidetes represent the most abundant phylum, followed by Firmicutes [11,12]. In
Microbial–host interactions and innate immunity, inflammation
The relationship between microbes and the innate immune system in the gastrointestinal tract has been reviewed [56,57]. Intestinal cells including the intestinal epithelium harbor receptors to microbial components, TLRs, which play a major role in innate immunity [26,58]. Activation of these Toll-like receptors results in signaling cascades that induce nuclear translocation of nuclear factor kappa-β (NFKβ), a transcription factor that induced transcription of various pro- and anti-inflammatory
Metabolome in necrotizing enterocolitis
Microbiota-derived metabolites, short chain fatty acids (SCFAs), butyrate, propionate and acetate induce IL-18 production from the intestinal epithelial cells (IECs) through activation of NOD-like family, receptors (NLRs) [65]. Acetate produced by Bifidobacteria promotes epithelial cell barrier function by inducing an anti-apoptotic response in the IECs. Microbiota-derived sphingolipids presented on CD1d by dendritic cells inhibit colonic invariant natural killer T-cell development. Thus
Future directions
For the prediction and diagnosis of NEC, diagnostic biomarkers include those that may not be specific for NEC such as the C-reactive protein, white blood cell count, and platelet count. However, more specific biomarkers are being developed which include tight junction proteins such as claudin-3, intestinal epithelial cell proteins such as intestinal fatty acid binding protein (IFAB), both of which can be analyzed non-invasively in the urine. More predictive biomarkers using the proteomic,
Conflicts of interest
None declared.
Funding sources
None.
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2022, Journal of Surgical ResearchCitation Excerpt :Neonatal necrotizing enterocolitis (NEC) is a common and devastating disease in neonates.1 The precise pathogenesis of NEC remains unknown, but premature birth, an imbalance in microvascular tone, and gut dysbiosis have been implicated.2,3 Accumulating data suggest that gut dysbiosis plays a vital role in developing NEC; hence, maintaining gut microbiota homeostasis is necessary to prevent NEC.
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