Abstract
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.
Highlights
Necrotizing enterocolitis (NEC) is one of the most common and serious diseases of the digestive system of newborns
In the NEC+butyrate group, one death occurred on the 1st day, two deaths occurred on the 2nd day, and three deaths occurred on the 3rd day
The results show that butyrate administration modulates the intestinal flora composition by increasing the beneficial flora Lactobacillus [30] and decreasing the harmful bacteria Enterococcus, similar to the results reported by Li et al [31]
Summary
Necrotizing enterocolitis (NEC) is one of the most common and serious diseases of the digestive system of newborns. This disease mainly occurs in premature and low-birth-weight infants, with an occurrence rate of approximately 9–13%, seriously affecting the survival and long-term prognosis of children [1]. In the past 50 years, the overall survival rate has not changed significantly, with an average mortality rate of 20–30% for infants with NEC and 50% for those requiring surgical treatment [2]. NEC is caused by multiple factors, and an excessive intestinal inflammatory response and altered microbiota are both important in the pathogenesis of this disease [3]. In NEC infants, the intestinal flora diversity is often lower than that in unaffected infants and is mainly characterized by an increase in the relative abundance of Proteobacteria and a decrease in the relative abundance of Firmicutes and Bacteroides [5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
