"beta-glucan protects against necrotizing enterocolitis in mice by inhibiting intestinal inflammation, improving the gut barrier, and modulating gut microbiota"
作者全名："Zhang, Xingdao; Zhang, Yuni; He, Yu; Zhu, Xingwang; Ai, Qing; Shi, Yuan"
作者地址："[Zhang, Xingdao; Zhang, Yuni; He, Yu; Zhu, Xingwang; Ai, Qing; Shi, Yuan] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Dept Neonatol,Key Lab Child Dev & Diso, Chongqing, Peoples R China; [Zhang, Xingdao; Zhang, Yuni; He, Yu; Zhu, Xingwang; Ai, Qing; Shi, Yuan] Chongqing Key Lab Pediat, Chongqing, Peoples R China"
通信作者："Shi, Y (通讯作者)，Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Dept Neonatol,Key Lab Child Dev & Diso, Chongqing, Peoples R China.; Shi, Y (通讯作者)，Chongqing Key Lab Pediat, Chongqing, Peoples R China."
来源：JOURNAL OF TRANSLATIONAL MEDICINE
关键词：beta-glucan; Inflammatory cytokines; Tight junctions; Intestinal microbiota; TLR4-NF-kappa B
摘要："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. beta-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of beta-glucan on NEC.Methods Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and beta-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml beta-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-kappa B 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 beta-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-kappa B, IL-1 beta, IL-6, and TNF-alpha; 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 beta-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 beta-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-kappa B signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota."
基金机构："2020 General Project of Clinical Medical Research, National Clinical Medical Research Center for Children's Health and Disease [NCRCCHD-2020-GP-03]; special key project of technology innovation and application development of Chongqing Science and Technology Bureau [CSTC2021jscx-gksb-N0015]; National Natural Science Foundation of China ; Science and health project of Chongqing Health Commission [2020FYYX217]"
基金资助正文："This work was supported by 2020 General Project of Clinical Medical Research, National Clinical Medical Research Center for Children's Health and Disease (NCRCCHD-2020-GP-03), the special key project of technology innovation and application development of Chongqing Science and Technology Bureau (CSTC2021jscx-gksb-N0015), National Natural Science Foundation of China (NO.82001602), Science and health project of Chongqing Health Commission (NO.2020FYYX217)."