Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis

Objective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and ar...

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Main Authors: Qian Sun, Yan-Chun Ji, Zheng-Li Wang, Xiang She, Yu He, Qing Ai, Lu-Quan Li
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/6259381
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author Qian Sun
Yan-Chun Ji
Zheng-Li Wang
Xiang She
Yu He
Qing Ai
Lu-Quan Li
author_facet Qian Sun
Yan-Chun Ji
Zheng-Li Wang
Xiang She
Yu He
Qing Ai
Lu-Quan Li
author_sort Qian Sun
collection DOAJ
description Objective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. Results. Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1β, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 (P<0.05). Treatment with butyrate decreased the proportion of opportunistic Clostridium_sensu_stricto_1 and Enterococcus and increased the proportion of beneficial Firmicutes and Lactobacillus in the NEC model. Conclusions. Sodium butyrate intervention relieves intestinal inflammation and partially corrects the disrupted intestinal flora in mice with NEC.
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spelling doaj-art-246ee1b552d4408aa65e126c35c2f6dd2025-08-20T02:04:41ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/62593816259381Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing EnterocolitisQian Sun0Yan-Chun Ji1Zheng-Li Wang2Xiang She3Yu He4Qing Ai5Lu-Quan Li6Department of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaDepartment of Neonatology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaObjective. To determine the role of sodium butyrate in intestinal inflammation via regulation of high-mobility group box-1 (HMGB1), we analyzed the potential mechanism in necrotizing enterocolitis (NEC) in a neonatal mouse model. Methods. A NEC model was created with hypoxia and cold exposure and artificial overfeeding. C57BL/6 neonatal mice were randomized into three groups: the control, untreated NEC, and sodium butyrate (150 mM)-pretreated NEC groups. Pathological variations in ileocecal intestinal tissue were observed by HE staining and scored in a double-blind manner. The mRNA expression levels of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and inflammatory cytokines in intestinal tissues were determined by quantitative real-time PCR. The protein levels of HMGB1 and associated cytokines in intestinal tissues were evaluated using ELISA. The relative protein expression levels of TLR4 and NF-κB in intestinal tissues were quantified by western blot. Results. Sodium butyrate administration improved the body weight and survival rate of NEC mice; relieved intestinal pathological injury; reduced the intestinal expression of HMGB1, TLR4, NF-κB, interleukin- (IL-) 1β, IL-6, IL-8, and TNF-α; and increased the intestinal expression of IL-10 (P<0.05). Treatment with butyrate decreased the proportion of opportunistic Clostridium_sensu_stricto_1 and Enterococcus and increased the proportion of beneficial Firmicutes and Lactobacillus in the NEC model. Conclusions. Sodium butyrate intervention relieves intestinal inflammation and partially corrects the disrupted intestinal flora in mice with NEC.http://dx.doi.org/10.1155/2021/6259381
spellingShingle Qian Sun
Yan-Chun Ji
Zheng-Li Wang
Xiang She
Yu He
Qing Ai
Lu-Quan Li
Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
Mediators of Inflammation
title Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
title_full Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
title_fullStr Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
title_full_unstemmed Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
title_short Sodium Butyrate Alleviates Intestinal Inflammation in Mice with Necrotizing Enterocolitis
title_sort sodium butyrate alleviates intestinal inflammation in mice with necrotizing enterocolitis
url http://dx.doi.org/10.1155/2021/6259381
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