Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators

Neu, Josef; Pammi, Mohan

doi:10.1016/j.siny.2018.08.001

Cited by 68 publications

(52 citation statements)

References 81 publications

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“…Keywords: VEGF, IL-18, IL-4 receptor α-chain, polymorphisms, necrotizing enterocolitis, preterm INTRODUCTION Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality from gastrointestinal disease in very and extremely preterm infants (1,2). As extensively discussed in several exhaustive reviews, the etiology of NEC is multifactorial and largely related to immaturity of the gastrointestinal tract (1)(2)(3)(4)(5)(6)(7)(8)(9). Besides low gestational age (GA), a complex interplay of other factors, such as type of feeding, gut dysbiosis, the high susceptibility of intestinal mucosal surface to inflammatory processes, or intestinal hypoperfusion may contribute to the pathogenesis of NEC (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

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confidence: 99%

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G: A Validation Study in a Prospective Multicenter Cohort

et al. 2020

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The etiology of necrotizing enterocolitis (NEC) is multifactorial and an underlying genetic predisposition to NEC is increasingly being recognized. A growing number of studies identified single nucleotide polymorphisms (SNPs) of selected genes with potential biological relevance in the development of NEC. However, few of these genetic studies have been replicated in validation cohorts. We aimed to confirm in a cohort of 358 preterm newborns (gestational age <30 weeks, 26 cases of NEC ≥ Bell stage II) the association with NEC of three candidate SNPs: the vascular endothelium growth factor (VEGF) C-2578A polymorphism (rs699947), the interleukin (IL)-18 C-607A polymorphism (rs1946518), and the IL-4 receptor α-chain (IL-4Rα) A-1902G polymorphism (rs1801275). We observed that allele and genotype frequencies of the three SNPs did not significantly differ between the infants with and without NEC. In contrast, the minor G-allele of the IL-4Rα A-1902G polymorphism was significantly less frequent in the group of 51 infants with the combined outcome NEC or death before 34 weeks postmenstrual age than in the infants without the outcome (0.206 vs. 0.331, P = 0.01). In addition, a significant negative association of the G-allele with the combined outcome NEC or death was found using the dominant (adjusted odds ratio, aOR: 0.44, 95% CI 0.21-0.92), recessive (aOR 0.15, 95% CI 0.03-0.74), and additive (aOR 0.46, 95% CI 0.26-0.80) genetic models. In conclusion our study provides further evidence that a genetic variant of the IL-4Rα gene may contribute to NEC.

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confidence: 99%

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G: A Validation Study in a Prospective Multicenter Cohort

et al. 2020

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“…This suggests that the microbiota of formula-fed infants may be more susceptible to environmental factors. The fact that preterm infants who were fed exclusively breast milk have a lower risk of NEC may be based on the fact that, besides the fact that breast milk contains specific macronutrients, polyunsaturated fatty acids, lactoferrin, immune cells, and immunoglobulins, it also contains microbes that appear to be personalized for each mother-infant pair [7]. …”

Section: Microbiota and Necmentioning

confidence: 99%

“…Activation of IL-8 attracts immune cells (neutrophils) to trigger areas of the intestine where they undergo phagocytosis and other inflammatory responses that cause vasoconstriction, ischemia, and injury to the intestine (Fig. 1) [7, 40]. …”

Section: Microbiota and Necmentioning

confidence: 99%

“…Besides, the beta-oxidation of butyrate leads to a low oxygen and nitrate environment in the gut, which helps to prevent dysbiosis [43]. Dysbiosis may disturb the balance in SCFA content in the gut [7]; however, the exact mechanisms have not been elucidated and may be contradictory since both high and low intestinal SCFA levels are associated with NEC (Fig. 1) [39, 44].…”

Section: Microbiota and Necmentioning

confidence: 99%

“…Although no single pathogen has been identified to cause NEC, there has been an increasing understanding of the relation between overall gut microbiota, compositional alterations referred to as dysbiosis, and NEC [5, 7]. The recognition of NEC-specific dysbiosis and/or the alteration of the microbiota may allow for a timely diagnosis, targeted treatment, and possibly even prevention or treatment of NEC.…”

Section: Introductionmentioning

confidence: 99%

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Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

et al. 2019

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Necrotizing enterocolitis (NEC) is a relatively common disease in very-low-birth-weight infants and is associated with high mortality and morbidity. In survivors, neurodevelopmental impairment is frequently seen. The exact etiology remains largely to be elucidated, but microbiota are considered to play a major role in the development of NEC. Furthermore, emerging evidence exists that the microbiota is also of importance in brain function and development. Therefore, microbiota characterization has not only potential as a diagnostic or even preventive tool to predict NEC, but may also serve as a biomarker to monitor and possibly even as a target to manipulate brain development. Analysis of fecal volatile organic compounds, which shape the volatile metabolome and reflect microbiota function and host interaction, has been shown to be of interest in the diagnosis of NEC and late-onset sepsis. In this review, we discuss evidence of the role of the complex interplay between microbiota, NEC, and brain development, including the brain-gut axis in preterm infants.

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Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes

et al. 2020

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Key Points Question What are the long-term outcomes associated with dysbiosis of gut microbiota in very preterm newborns? Findings In this cohort study of 577 very preterm newborns across 24 neonatal intensive care units from a French nationwide cohort, gut microbiota at week 4 after birth showed 6 bacterial patterns that varied according to gestational age, perinatal characteristics, individual treatments, and neonatal intensive care unit strategies. Three clusters were associated with 2-year outcomes after adjustment for these confounders. Meaning Modifying strategies associated with alterations in microbiota, such as promoting enteral nutrition, reducing sedation use, promoting early extubation, or skin-to-skin practice, may be correlated with outcomes in preterm newborns.

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Necrotizing enterocolitis: The intestinal microbiome, metabolome and inflammatory mediators

Cited by 68 publications

References 81 publications

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G: A Validation Study in a Prospective Multicenter Cohort

Risk of Necrotizing Enterocolitis Associated With the Single Nucleotide Polymorphisms VEGF C-2578A, IL-18 C-607A, and IL-4 Receptor α-Chain A-1902G: A Validation Study in a Prospective Multicenter Cohort

Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

Assessment of Neonatal Intensive Care Unit Practices and Preterm Newborn Gut Microbiota and 2-Year Neurodevelopmental Outcomes

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