异丁酸盐通过猪宿主-微生物群相互作用增强对炎症性肠病的抵抗力。

IF 11 1区 综合性期刊 Q1 Multidisciplinary
Research Pub Date : 2025-05-08 eCollection Date: 2025-01-01 DOI:10.34133/research.0673
Xiuyu Fang, Haiyang Liu, Junling Liu, Yongqing Du, Zihan Chi, Yiqi Bian, Xuan Zhao, Teng Teng, Baoming Shi
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引用次数: 0

摘要

补充短链脂肪酸(SCFAs)是一种潜在的治疗炎症性肠病(IBD)的方法。然而,异丁酸酯在IBD中的治疗效果和作用机制尚不清楚。临床数据表明,克罗恩病患者粪便中的异丁酸盐水平明显低于健康对照组。与健康小鼠和健康猪相比,结肠炎小鼠和猪的异丁酸水平显著降低。此外,猪体内异丁酸水平与疾病活动指数呈显著负相关。我们推测异丁酸盐可能在调节宿主肠道稳态中起关键作用。建立了具有类似人类胃肠道结构和功能的葡聚糖硫酸钠诱导猪结肠炎模型;我们进行了多组学分析,从动物和细胞水平研究了异丁酸酯对IBD的治疗效果和潜在机制,并验证了结果。从表型上看,异丁酸盐能显著缓解猪结肠炎引起的腹泻、便血、体重减轻和结肠缩短。从机制上看,异丁酸盐可以增加reuteri乳杆菌的相对丰度,从而增加吲哚-3-乳酸的产生,调节芳香烃受体的表达和下游信号通路,调节Foxp3+ CD4+ T细胞募集,从而缓解结肠炎。异丁酸盐可以直接激活G蛋白偶联受体109A,促进Claudin-1的表达,改善肠道屏障功能。此外,异丁酸可增加肠道SCFAs和3-羟基丁酸的生成,抑制TLR4/MyD88/NF-κB信号通路,抑制肠道炎症。总之,我们的研究结果表明,异丁酸盐通过宿主-微生物群相互作用赋予了对IBD的抗性,为使用异丁酸盐缓解结肠炎提供了理论基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Isobutyrate Confers Resistance to Inflammatory Bowel Disease through Host-Microbiota Interactions in Pigs.

Supplementation with short-chain fatty acids (SCFAs) is a potential therapeutic approach for inflammatory bowel disease (IBD). However, the therapeutic effects and mechanisms of action of isobutyrate in IBD remain unclear. Clinical data indicate that the fecal levels of isobutyrate are markedly lower in patients with Crohn's disease than in healthy controls. Compared with healthy mice and healthy pigs, mice and pigs with colitis presented significantly lower isobutyrate levels. Furthermore, the level of isobutyrate in pigs was significantly negatively correlated with the disease activity index. We speculate that isobutyrate may play a crucial role in regulating host gut homeostasis. We established a model of dextran sulfate sodium-induced colitis in pigs, which have gastrointestinal structure and function similar to those of humans; we performed multiomic analysis to investigate the therapeutic effects and potential mechanisms of isobutyrate on IBD at both the animal and cellular levels and validated the results. Phenotypically, isobutyrate can significantly alleviate diarrhea, bloody stools, weight loss, and colon shortening caused by colitis in pigs. Mechanistically, isobutyrate can increase the relative abundance of Lactobacillus reuteri, thereby increasing the production of indole-3-lactic acid, regulating aryl hydrocarbon receptor expression and downstream signaling pathways, and regulating Foxp3+ CD4+ T cell recruitment to alleviate colitis. Isobutyrate can directly activate G protein-coupled receptor 109A, promote the expression of Claudin-1, and improve intestinal barrier function. In addition, isobutyrate can increase the production of intestinal SCFAs and 3-hydroxybutyric acid and inhibit the TLR4/MyD88/NF-κB signaling pathway to suppress intestinal inflammation. In conclusion, our findings demonstrate that isobutyrate confers resistance to IBD through host-microbiota interactions, providing a theoretical basis for the use of isobutyrate in alleviating colitis.

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来源期刊
Research
Research Multidisciplinary-Multidisciplinary
CiteScore
13.40
自引率
3.60%
发文量
0
审稿时长
14 weeks
期刊介绍: Research serves as a global platform for academic exchange, collaboration, and technological advancements. This journal welcomes high-quality research contributions from any domain, with open arms to authors from around the globe. Comprising fundamental research in the life and physical sciences, Research also highlights significant findings and issues in engineering and applied science. The journal proudly features original research articles, reviews, perspectives, and editorials, fostering a diverse and dynamic scholarly environment.
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