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Nutritional Interventions of Necrotizing Enterocolitis in Newborns

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Immunology".

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 32346

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Special Issue Editor

Dr. Steven McElroy

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Guest Editor

Department of Pediatrics, Division of Neonatology, University of Iowa Children’s Hospital, Iowa, IA 52242, USA
Interests: necrotizing enterocolitis; paneth cells; antimicrobial peptides; intestinal development

Special Issue Information

Dear Colleagues,

Nutrients is planning a Special Issue focusing on Nutritional interventions for prevention or treatment of necrotizing enterocolitis (NEC). NEC remains a leading cause of morbidity and mortality in preterm infants with mortality rates remaining around 30%. While there are no current targeted treatments for NEC, recent advances in the field have made it clear that what an infant ingests can impact the risk of developing NEC. This Special Issue aims to bring together the latest research on the role of nutrition and nutritional supplements in preventing or impacting NEC. Specifically, this Special Issue will focus on the role of breast milk, donor breast milk, the various components in milk, and oral supplements that have been demonstrated to protect against NEC and other inflammatory diseases, as well as the impacts of nutrition or oral supplements on the microbiome and/or on the inflammatory response of the host. This issue seeks to provide a comprehensive composite of the advances in nutritional strategies that can modulate or prevent NEC.

Dr. Steven McElroy
Guest Editor

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Keywords

Necrotizing enterocolitis (NEC)
Human milk
Donor milk
Preterm nutrition
Innate immunity
Prematurity
Antimicrobial peptides
Inflammation
Probiotics

Published Papers (7 papers)

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Research

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19 pages, 2362 KiB

Open AccessArticle

Bifidobacterium longum Subspecies infantis Strain EVC001 Decreases Neonatal Murine Necrotizing Enterocolitis

by Shiloh R. Lueschow, Timothy J. Boly, Steven A. Frese, Giorgio Casaburi, Ryan D. Mitchell, Bethany M. Henrick and Steven J. McElroy

Nutrients 2022, 14(3), 495; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14030495 - 24 Jan 2022

Cited by 9 | Viewed by 3380

Abstract

Necrotizing enterocolitis (NEC) is a disease mainly of preterm infants with a 30–50% mortality rate and long-term morbidities for survivors. Treatment strategies are limited and have not improved in decades, prompting research into prevention strategies, particularly with probiotics. Recent work with the probiotic B. infantis EVC001 suggests that this organism may generate a more appropriate microbiome for preterm infants who generally have inappropriate gut colonization and inflammation, both risk factors for NEC. Experimental NEC involving Paneth cell disruption in combination with bacterial dysbiosis or formula feeding was induced in P14-16 C57Bl/6 mice with or without gavaged B. infantis. Following completion of the model, serum, small intestinal tissue, the cecum, and colon were harvested to examine inflammatory cytokines, injury, and the microbiome, respectively. EVC001 treatment significantly decreased NEC in a bacterial dysbiosis dependent model, but this decrease was model-dependent. In the NEC model dependent on formula feeding, no difference in injury was observed, but trending to significant differences was observed in serum cytokines. EVC001 also improved wound closure at six and twelve hours compared to the sham control in intestinal epithelial monolayers. These findings suggest that B. infantis EVC001 can prevent experimental NEC through anti-inflammatory and epithelial barrier restoration properties. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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17 pages, 5365 KiB

Open AccessArticle

Untargeted Metabolomic Analysis of Human Milk from Mothers of Preterm Infants

by Lila S. Nolan, Angela N. Lewis, Qingqing Gong, James J. Sollome, Olivia N. DeWitt, Robert D. Williams and Misty Good

Nutrients 2021, 13(10), 3604; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13103604 - 14 Oct 2021

Cited by 10 | Viewed by 3525

Abstract

The application of metabolomics in neonatology offers an approach to investigate the complex relationship between nutrition and infant health. Characterization of the metabolome of human milk enables an investigation into nutrients that affect the neonatal metabolism and identification of dietary interventions for infants at risk of diseases such as necrotizing enterocolitis (NEC). In this study, we aimed to identify differences in the metabolome of breast milk of 48 mothers with preterm infants with NEC and non-NEC healthy controls. A minimum significant difference was observed in the human milk metabolome between the mothers of infants with NEC and mothers of healthy control infants. However, significant differences in the metabolome related to fatty acid metabolism, oligosaccharides, amino sugars, amino acids, vitamins and oxidative stress-related metabolites were observed when comparing milk from mothers with control infants of ≤1.0 kg birth weight and >1.5 kg birth weight. Understanding the functional biological features of mothers’ milk that may modulate infant health is important in the future of tailored nutrition and care of the preterm newborn. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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22 pages, 2805 KiB

Open AccessArticle

Comparative Genome Analysis of Bifidobacterium longum subsp. infantis Strains Reveals Variation in Human Milk Oligosaccharide Utilization Genes among Commercial Probiotics

by Rebbeca M. Duar, Giorgio Casaburi, Ryan D. Mitchell, Lindsey N.C. Scofield, Camila A. Ortega Ramirez, Daniela Barile, Bethany M. Henrick and Steven A. Frese

Nutrients 2020, 12(11), 3247; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12113247 - 23 Oct 2020

Cited by 41 | Viewed by 10492

Abstract

Dysbiosis is associated with acute and long-term consequences for neonates. Probiotics can be effective in limiting the growth of bacteria associated with dysbiosis and promoting the healthy development of the infant microbiome. Given its adaptation to the infant gut, and promising data from animal and in vitro models, Bifidobacterium longum subsp. infantis is an attractive candidate for use in infant probiotics. However, strain-level differences in the ability of commercialized strains to utilize human milk oligosaccharides (HMOs) may have implications in the performance of strains in the infant gut. In this study, we characterized twelve B. infantis probiotic strains and identified two main variants in one of the HMO utilization gene clusters. Some strains possessed the full repertoire of HMO utilization genes (H5-positive strains), while H5-negative strains lack an ABC-type transporter known to bind core HMO structures. H5-positive strains achieved significantly superior growth on lacto-N-tetraose and lacto-N-neotetraose. In vitro, H5-positive strains had a significant fitness advantage over H5-negative strains, which was also observed in vivo in breastfed infants. This work provides evidence of the functional implications of genetic differences among B. infantis strains and highlights that genotype and HMO utilization phenotype should be considered when selecting a strain for probiotic use in infants. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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Review

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30 pages, 1406 KiB

Open AccessReview

The Role of Dietary Fats in the Development and Prevention of Necrotizing Enterocolitis

by Belal N. Alshaikh, Adriana Reyes Loredo, Megan Knauff, Sarfaraz Momin and Shirin Moossavi

Nutrients 2022, 14(1), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14010145 - 29 Dec 2021

Cited by 4 | Viewed by 3057

Abstract

Necrotizing enterocolitis (NEC) is a significant cause of mortality and morbidity in preterm infants. The pathogenesis of NEC is not completely understood; however, intestinal immaturity and excessive immunoreactivity of intestinal mucosa to intraluminal microbes and nutrients appear to have critical roles. Dietary fats are not only the main source of energy for preterm infants, but also exert potent effects on intestinal development, intestinal microbial colonization, immune function, and inflammatory response. Preterm infants have a relatively low capacity to digest and absorb triglyceride fat. Fat may thereby accumulate in the ileum and contribute to the development of NEC by inducing oxidative stress and inflammation. Some fat components, such as long-chain polyunsaturated fatty acids (LC-PUFAs), also exert immunomodulatory roles during the early postnatal period when the immune system is rapidly developing. LC-PUFAs may have the ability to modulate the inflammatory process of NEC, particularly when the balance between n3 and n6 LC-PUFAs derivatives is maintained. Supplementation with n3 LC-PUFAs alone may have limited effect on NEC prevention. In this review, we describe how various fatty acids play different roles in the pathogenesis of NEC in preterm infants. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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15 pages, 702 KiB

Open AccessReview

Human Milk Growth Factors and Their Role in NEC Prevention: A Narrative Review

by Daniel J. York, Anne L. Smazal, Daniel T. Robinson and Isabelle G. De Plaen

Nutrients 2021, 13(11), 3751; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13113751 - 23 Oct 2021

Cited by 15 | Viewed by 3346

Abstract

Growing evidence demonstrates human milk’s protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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12 pages, 506 KiB

Open AccessReview

Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis

by Ameer Al-Hadidi, Jason Navarro, Steven D. Goodman, Michael T. Bailey and Gail E. Besner

Nutrients 2021, 13(3), 918; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13030918 - 12 Mar 2021

Cited by 18 | Viewed by 3526

Abstract

Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate’s vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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19 pages, 414 KiB

Open AccessReview

Lipid Composition, Digestion, and Absorption Differences among Neonatal Feeding Strategies: Potential Implications for Intestinal Inflammation in Preterm Infants

by Kathryn Burge, Frederico Vieira, Jeffrey Eckert and Hala Chaaban

Nutrients 2021, 13(2), 550; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020550 - 08 Feb 2021

Cited by 10 | Viewed by 4114

Abstract

Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality in the neonatal population. Formula feeding is among the many risk factors for developing the condition, a practice often required in the cohort most often afflicted with NEC, preterm infants. While the virtues of many bioactive components of breast milk have been extolled, the ability to digest and assimilate the nutritional components of breast milk is often overlooked. The structure of formula differs from that of breast milk, both in lipid composition and chemical configuration. In addition, formula lacks a critical digestive enzyme produced by the mammary gland, bile salt-stimulated lipase (BSSL). The gastrointestinal system of premature infants is often incapable of secreting sufficient pancreatic enzymes for fat digestion, and pasteurization of donor milk (DM) has been shown to inactivate BSSL, among other important compounds. Incompletely digested lipids may oxidize and accumulate in the distal gut. These lipid fragments are thought to induce intestinal inflammation in the neonate, potentially hastening the development of diseases such as NEC. In this review, differences in breast milk, pasteurized DM, and formula lipids are highlighted, with a focus on the ability of those lipids to be digested and subsequently absorbed by neonates, especially those born prematurely and at risk for NEC. Full article

(This article belongs to the Special Issue Nutritional Interventions of Necrotizing Enterocolitis in Newborns)

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