scholarly journals Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Steven X. Cho ◽  
Ina Rudloff ◽  
Jason C. Lao ◽  
Merrin A. Pang ◽  
Rimma Goldberg ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Lymphoid Cells ◽  
Immune Homeostasis ◽  
Blood Monocytes ◽  
Type 3 ◽  
Lower Birthweight ◽  
Novel Therapeutic

AbstractNecrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/TH17 polarization. In murine NEC, pro-inflammatory type 3 NKp46−RORγt+Tbet+ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46+RORγt+ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies.

scholarly journals Low Microbial Diversity and Abnormal Microbial Succession Is Associated with Necrotizing Enterocolitis in Preterm Infants

2017 ◽  
Vol 8 ◽  
Author(s):  
Priscila T. Dobbler ◽  
Renato S. Procianoy ◽  
Volker Mai ◽  
Rita C. Silveira ◽  
Andréa L. Corso ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Microbial Succession

scholarly journals Necrotizing enterocolitis and the microbiome: Current status and future directions

2020 ◽  
Author(s):  
Robert Thänert ◽  
Eric C Keen ◽  
Gautam Dantas ◽  
Barbara B Warner ◽  
Phillip I Tarr
Keyword(s):  
Risk Factors ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Clinical Characteristics ◽  
Gastrointestinal Disorder ◽  
Current Status ◽  
Future Directions ◽  
Barrier Integrity ◽  
Microbial Dysbiosis

Abstract Decades of research have failed to define the pathophysiology of necrotizing enterocolitis (NEC), a devastating pediatric gastrointestinal disorder of preterm infants. However, recent evidence suggests that host-microbiota interactions, in which microbial dysbiosis is followed by loss of barrier integrity, inflammation, and necrosis, are central to NEC development. Thus, greater knowledge of the preterm infant microbiome could accelerate attempts to diagnose, treat, and prevent NEC. Here, we summarize clinical characteristics of and risk factors for NEC, the structure of the pre-event NEC microbiome, how this community interfaces with host immunology, and microbiome-based approaches that might prevent or lessen the severity of NEC in this very vulnerable population.

scholarly journals The Risk of Necrotizing Enterocolitis following the Administration of Hyperosmolar Enteral Medications to Extremely Preterm Infants

Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Faiza Latheef ◽  
Hanna Wahlgren ◽  
Helene Engstrand Lilja ◽  
Barbro Diderholm ◽  
Mattias Paulsson
Keyword(s):  
Clinical Practice ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Neonatal Intensive Care ◽  
Significant Risk ◽  
Quality Register ◽  
Increased Risk ◽  
Extremely Preterm ◽  
Extremely Preterm Infants ◽  
Hyperosmolar Solutions

<b><i>Introduction:</i></b> Necrotizing enterocolitis (NEC) is a disease predominantly affecting preterm infants. The administration of hyperosmolar solutions could lead to the development of NEC. The objective of this study was to measure the osmolality of enteral medications used in clinical practice and to assess the risk of NEC following exposure to hyperosmolar medications. <b><i>Methods:</i></b> A retrospective cohort study in extremely preterm infants (gestational age &#x3c;28 weeks) born between 2010 and 2016 at a tertiary neonatal intensive care unit in Sweden. 465 infants were identified via the Swedish Neonatal Quality register. Data relating to enteral administrations received during a two-week period were collected from the medical records. The osmolalities of medications were measured using an osmometer. Logistic regression was used to calculate the odds ratio of developing NEC. <b><i>Results:</i></b> A total of 253 patients met the inclusion criteria. The osmolalities of 5 commonly used medications significantly exceeded the recommended limit of 450 mOsm/kg set by the American Academy of Paediatrics (AAP). Most patients (94%) received at least one hyperosmolar medication. No significant risk of developing NEC could be found. <b><i>Conclusion:</i></b> The medications used in clinical practice can significantly exceed the limit set by the AAP. This study does not indicate an increased risk of developing NEC in extremely preterm infants following exposure to hyperosmolar medications. Further studies in larger cohorts are needed to determine the specific cut-off level of osmolality in relation to the pathogenesis of NEC.

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