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

Abstract

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.

The Nonbacterial Microbiome: Fungal and Viral Contributions to the Preterm Infant Gut in Health and Disease

“…Zhang et al evaluated the ability of the S. cerevisiae cell wall component, β-glucan, to protect against murine NEC. Pretreatment with β-glucan for 7 d reduced gut permeability, ameliorated intestinal inflammation, and induced beneficial changes to the bacterial microbiome via modulation of the TLR4/NF-κB pathway [194]. These results, in combination with an earlier study indicating β-glucan reduces inflammation in a neonatal rat NEC model [195], show promise in the ability of fungal components to constrain intestinal inflammation in the preterm infant population.…”

Intranasal administration with recombinant vaccine PRVXJ-delgE/gI/TK-S induces strong intestinal mucosal immune responses against PDCoV

“…PRV is an ideal vector for recombinant vaccines. Extensive research has involved the insertion of foreign antigen genes into the non-essential genes of gE, gI, and TK deletion PRV strains to construct recombinant vaccines, which have demonstrated the ability to provide multiple protection against PRV and other pathogens [ 25 , 26 ]. In a previous study, a recombinant PRV rPRVXJ-delgE/gI/TK-S that expresses PDCoV was developed.…”

A graded neonatal mouse model of necrotizing enterocolitis demonstrates that mild enterocolitis is sufficient to activate microglia and increase cerebral cytokine expression

“…Therefore, worsening degrees of intestinal inflammation in our enterocolitis model led to increasing cytokine and chemokine expression in the liver, which is the first major organ downstream of intestines. Other NEC animal models have demonstrated increases in cytokine levels of IL-6, IL-8, TNF-α, and IFN-γ as well 11,27 . With our model, we are able to distinguish cytokine levels between mild, moderate and severe NEC.…”