Butyrate suppresses experimental necrotizing enterocolitis-induced brain injury in mice.
Butyrate suppresses experimental necrotizing enterocolitis-induced brain injury in mice.
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丁酸盐可抑制实验性坏死性小肠结肠炎引起的小鼠脑损伤。
DOI：
10.3389/fped.2023.1284085
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发表时间：
2023
影响因子：
2.6
通讯作者：
中科院分区：
文献类型：
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作者：
坏死性小肠结肠炎（NEC）是早产儿的一种毁灭性疾病，50%的手术NEC婴儿发展为神经发育缺陷。NEC诱导的细胞因子释放和脑中炎性细胞活化介导神经元损伤的机制，以及肠内免疫治疗是否减弱NEC相关的脑损伤仍有待研究。基于我们先前的工作，这表明，实验NEC样肠损伤是衰减的短链脂肪酸，丁酸盐，在这项研究中，我们假设，NEC诱导的脑损伤将抑制肠内丁酸补充。使用标准化NEC小鼠模型[肠内配方喂养、脂多糖（LPS）和缺氧]。将小鼠随机分为以下组：对照组、NEC组、丁酸盐预处理的NEC组和丁酸盐对照组。使用经验证的评分系统对回肠切片进行NEC评分（1-4分，4分代表严重损伤）。肠和脑裂解物用于评估炎症、促炎信号传导和细胞凋亡。补充丁酸盐可减轻NEC引起的肠损伤。丁酸盐抑制了NEC诱导的大脑皮质和海马小胶质细胞活化。NEC增加了活化的小胶质细胞的数量，但减少了少突胶质细胞的数量。丁酸预处理减弱了这些变化。丁酸盐抑制NEC观察到的促炎性Toll样受体信号传导、细胞因子表达以及大脑皮层中GFAP和IBA 1诱导的增加的活化。实验NEC在大脑的几个区域中诱导炎症和小胶质细胞的活化，最显著的是在皮质中。丁酸盐预处理可抑制NEC诱导的神经炎症。在饮食中添加短链脂肪酸可用于减轻早产儿NEC诱导的肠道损伤和神经炎症。
Necrotizing enterocolitis (NEC) is a devastating disease in premature infants, and 50% of infants with surgical NEC develop neurodevelopmental defects. The mechanisms by which NEC-induced cytokine release and activation of inflammatory cells in the brain mediate neuronal injury, and whether enteral immunotherapy attenuates NEC-associated brain injury remain understudied. Based on our prior work, which demonstrated that experimental NEC-like intestinal injury is attenuated by the short-chain fatty acid, butyrate, in this study, we hypothesize that NEC-induced brain injury would be suppressed by enteral butyrate supplementation. A standardized NEC mouse model [enteral formula feeding, lipopolysaccharide (LPS), and hypoxia] was used. Mice were randomized into the following groups: control, NEC, butyrate pretreated NEC, and butyrate control. NEC scoring (1–4 with 4 representing severe injury) was performed on ileal sections using a validated scoring system. Intestinal and brain lysates were used to assess inflammation, proinflammatory signaling, and apoptosis. NEC-induced intestinal injury was attenuated by butyrate supplementation. NEC-induced microglial activation in the cerebral cortex and hippocampus was suppressed with butyrate. NEC increased the number of activated microglial cells but decreased the number of oligodendrocytes. Butyrate pretreatment attenuated these changes. Increased activation of proinflammatory Toll-like receptor signaling, cytokine expression, and induction of GFAP and IBA1 in the cerebral cortex observed with NEC was suppressed with butyrate. Experimental NEC induced inflammation and activation of microglia in several regions of the brain, most prominently in the cortex. NEC-induced neuroinflammation was suppressed with butyrate pretreatment. The addition of short-chain fatty acids to diet may be used to attenuate NEC-induced intestinal injury and neuroinflammation in preterm infants.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
影响因子：
2.4
作者：
Liu, Jia;Zhu, Haitao;Pierro, Agostino
通讯作者：
Pierro, Agostino
影响因子：
2.9
作者：
Berken, Jonathan A. A.;Chang, Jill
通讯作者：
Chang, Jill
DOI：
10.1038/nrgastro.2016.119
发表时间：
2016-10
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
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