The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review

Burge, Kathryn; Bergner, Erynn M.; Gunasekaran, Aarthi; Eckert, Jeffrey; Chaaban, Hala

doi:10.3390/nu12020546

Cited by 15 publications

(6 citation statements)

References 194 publications

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“…Numerous intestinal bacteria combine with intestinal epithelial cells to construct a strong barrier, which have the ability to resist the invasion of pathogens colonized in the intestinal tracts [ 57 ]. However, various prenatal or postnatal risk factors lead to a decreased diversity in gut microbiota, which disturbs the structure of gut microbiota and leads to a weak capacity of the intestinal barrier against potential pathogens in infants with NEC [ 58 , 59 ]. In addition, the metabolites released by pathogenic bacteria contribute to the destruction of the gut barrier and invasion by bacteria in the intestines, inducing an intestinal inflammation that finally leads to the occurrence of NEC [ 60 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

β-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota

Zhang

et al. 2023

J Transl Med

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Background Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and extremely low birth weight. β-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of β-glucan on NEC. Methods Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and β-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml β-glucan or phosphate buffer saline at 0.03 ml/g for 7 consecutive days before NEC induction and a NEC model was established with hypoxia combined with cold exposure and formula feeding. All the pups were killed after 72-h modeling. Hematoxylin–eosin staining was performed to assess the pathological injury to the intestines. The mRNA expression levels of inflammatory factors in intestinal tissues were determined using quantitative real-time PCR. The protein levels of TLR4, NF-κB and tight junction proteins in intestinal tissues were evaluated using western blotting and immunohistochemistry. 16S rRNA sequencing was performed to determine the structure of the gut microbiota. Results β-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-κB, IL-1β, IL-6, and TNF-α; increased the intestinal expression of IL-10; and improved the expression of ZO-1, Occludin and Claudin-1 within the intestinal barrier. Pre-treatment with β-glucan also increased the proportion of Actinobacteria, Clostridium butyricum, Lactobacillus johnsonii, Lactobacillus murinus, and Lachnospiraceae bacterium mt14 and reduced the proportion of Klebsiella oxytoca g Klebsiella in the NEC model. Conclusion β-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-κB signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota.

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Section: Discussionmentioning

confidence: 99%

β-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota

Zhang

et al. 2023

J Transl Med

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“…The proliferation and apoptosis, migration ability, and tight protein linkage of intestinal epithelial cells are important factors for maintaining the stable state of the epithelial cells. When NEC occurs, intestinal epithelial cells raise apoptosis, decrease proliferation ability, raise permeability, and decrease tight junction protein ZO-1 protein expression ( 31 ). After the homeostasis of intestinal epithelial cells is destroyed, the barrier dysfunction can result in intestinal damage while the repair of tissue damage is also an important process of fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Expression and Possible Role of Silent Mating Type Information Regulation 2 Homolog 1 in Post-necrotizing Enterocolitis Stricture in vivo and in vitro

Chen

Zhao

et al. 2022

Front. Pediatr.

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PurposeTo investigate the expression and possible role of Sirtuin1 or Silent mating–type information regulation 2 homolog-1 (SIRT1) in post-necrotizing enterocolitis stricture.Materials and MethodsThe expression characteristics of SIRT1 and TGF-β1 in post-necrotizing enterocolitis stricture were detected by immunohistochemistry. The siRNA-SIRT1 was used to inhibit the expression of SIRT1 in intestinal epithelial cells-6 (IEC-6), and qRT-PCR, WB, and ELISA were utilized to detect the changes of Transforming growth factor-β1 (TGF-β1), nuclear factor (NF)-κB, tumor necrosis factor-α (TNF-α), tight junction protein-1 (ZO-1), and vascular endothelial growth factor (VEGF) expressions. The IEC-6 cell proliferation and migration ability were tested via CCK8 kit and Transwell test. The expression of E-cadherin and Vimentin in cells was detected by immunofluorescence.ResultsThe CRP, IL-6, IL-10, and IFN-γ in the serum of Necrotizing enterocolitis (NEC) intestinal stenosis patients were significantly higher than the reference values. The SIRT1 protein was under-expressed and the TGF-β1 protein was overexpressed in NEC intestinal stenosis tissue. And the expression of SIRT1 was negatively correlated with TGF-β1. At the time of diagnosis of NEC, the expression of SIRT1 decreased in children with respiratory distress syndrome and CRP level increased. After inhibiting the expression of SIRT1 in IEC6 cells, the expression levels of TGF-β1, Smad3, and NF-κB were decreased, and the expression of ZO-1 was also decreased. The proliferation and migration ability of IEC6 cells was decreased significantly, and the expression of E-cadherin and Vimentin proteins in IEC6 cells did not change significantly.ConclusionPromotion of intestinal fibrosis by inflammation may be the mechanism of post-necrotizing enterocolitis stricture. SIRT1 may be a protective protein of NEC. The probable mechanism is that SIRT1 can regulate intestinal fibrosis and can protect the intestinal mucosal barrier function to participate in the process of post-necrotizing enterocolitis stricture.

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“…Numerous intestinal flora combine with intestinal epithelial cells to construct a strong 'fence', which can resist the invasion of pathogenic bacteria colonized (Kamada et al 2013). However, immature gastrointestinal tract and low diversity of intestinal flora in premature infants probably are weakly resisted to pathogenic bacteria colonized (Burge et al 2020). In NEC children, the intestinal flora is dominated by Gram-negative bacteria, such as Proteobacteria, which amplify the role of immature gastrointestinal tract and make the intestine more susceptible to inflammatory responses (Tarek et al 2018).…”

Section: The Action Mode Of Intestinal Flora On Nec Pathogenesismentioning

confidence: 99%

A mini-review of advances in intestinal flora and necrotizing enterocolitis

Zhao

Shi

Zhu

et al. 2022

Letters in Applied Microbiology

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Necrotizing enterocolitis (NEC) is a digestive disease that frequently occurs in premature infants with low gestational age and low birth weight, and seriously threatens the life of NEC patients. NEC pathogenesis is recognized to be affected by multiple factors, such as preterm birth, formula feeding and low birth weight. As a popular object for the past decades, intestinal flora is commonly used in NEC‐related studies, and intestinal disorder is considered as a critical risk factor for the occurrence and development of NEC. The colonization of abnormal microbiota into gastrointestinal micro‐ecosystem can easily lead to the damage of intestinal mucosal barrier, destruction of immune function, inflammatory reaction and further the occurrence of NEC. Although it is a low‐cost and safe way to prevent and treat the NEC by early intervention of oral probiotics to regulate the intestinal homoeostasis, more studies in the future are still encouraged to narrow the gap between theoretical guidance and practical application.

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The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review

Cited by 15 publications

References 194 publications

β-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota

β-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota

Expression and Possible Role of Silent Mating Type Information Regulation 2 Homolog 1 in Post-necrotizing Enterocolitis Stricture in vivo and in vitro

A mini-review of advances in intestinal flora and necrotizing enterocolitis

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