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婴幼儿乳糖不耐受的肠道菌群-短链脂肪酸轴机制研究

Study on the mechanism of the gut microbiota-short-chain fatty acids axis in lactose intolerance in infants
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摘要 目的探讨肠道菌群-短链脂肪酸轴在婴幼儿乳糖不耐受(LI)异质性中的作用机制。方法选取2024年6月至2025年4月在徐州医科大学附属医院因腹泻确诊LI的138例患儿为研究对象。根据LI的严重程度分为轻度LI组(n=68)和重度LI组(n=70),再选取同期50例健康保健儿童作为健康对照组。通过16S rRNA基因测序分析肠道菌群结构,气相色谱-质谱联用(GC-MS)定量粪便短链脂肪酸含量,建立婴儿肠道类器官模型验证关键短链脂肪酸的功能机制。结果与健康对照组比较,轻度LI组、重度LI组Shannon指数、双歧杆菌属丰度、双歧杆菌属与大肠埃希菌属丰度比值(B/E)更低,且重度LI组低于轻度LI组(P<0.05);与健康对照组比较,轻度LI组、重度LI组大肠埃希菌属/志贺菌属丰度更高,且重度LI组高于轻度LI组(P<0.05)。与健康对照组比较,轻度LI组和重度LI组总短链脂肪酸、乙酸、丙酸、丁酸水平更低,且重度LI组低于轻度LI组(P<0.05)。多元线性回归预测模型为腹泻频率=6.80-0.17×丁酸+0.25×大肠杆菌-0.31×双歧杆菌,该模型预测效能的曲线下面积为0.89(95%CI:0.83~0.94)。与对照肠细胞比较,乳糖处理的肠细胞跨上皮细胞层电阻(TEER)、紧密连接蛋白(Claudin)-3水平更低,IL-8水平更高,而乳糖+丁酸处理的肠细胞TEER、Claudin-3水平较乳糖处理的肠细胞更高,IL-8水平更低(P<0.05)。结论肠道菌群失衡与丁酸缺乏共同导致婴幼儿LI症状差异。 Objective To explore the mechanism of the gut microbiota-short-chain fatty acid axis in the heterogeneity of lactose intolerance(LI)in infants.Methods A total of 138 children diagnosed with LI due to diarrhea in the Affiliated Hospital of Xuzhou Medical University from June 2024 to April 2025 were selected as the research subjects.According to the severity of LI,they were divided into the mild LI group(n=68)and the severe LI group(n=70),and then 50 healthy children who received health care during the same period were selected as the healthy control group.The structure of the intestinal flora was analyzed by 16S rRNA gene sequencing,the content of short-chain fatty acids in feces was quantified by gas chromatography-mass spectrometry(GC-MS),and an infant intestinal organoid model was established to verify the functional mechanism of key short-chain fatty acids.Results Compared with the healthy control group,the Shannon index,the abundance of Bifidobacterium,and the ratio of Bifidobacterium to Escherichia coli abundance(B/E)in the mild LI group and the severe LI group were lower,and the severe LI group was lower than the mild LI group(P<0.05).Compared with the healthy control group,the Escherichia coli/Shigella abundance was higher in the mild LI group and the severe LI group,and the severe LI group was higher than the mild LI group(P<0.05).Compared with the healthy control group,the levels of total short-chain fatty acids,acetic acid,propionic acid and butyric acid in the mild LI group and the severe LI group were lower,and those in the severe LI group were lower than those in the mild LI group(P<0.05).The multiple linear regression prediction model showed that the frequency of diarrhea=6.80-0.17×butyric acid+0.25×Escherichia coli-0.31×Bifidobacterium.The area under the curve of the prediction efficacy of this model was 0.89(95%CI:0.83-0.94).Compared with the control intestinal cells,the levels of transepithelial layer resistance(TEER)and tight junction protein(Claudin)-3 in the intestinal cells treated with lactose were lower,and the level of IL-8 was higher.However,the levels of TEER and Claudin-3 in the intestinal cells treated with lactose+butyric acid were higher than those in the intestinal cells treated with lactose,and the level of IL-8 was lower(P<0.05).Conclusion The imbalance of intestinal flora and butyric acid deficiency jointly lead to the differences in LI symptoms in infants and young children.
作者 常煜胤 卢太苓 路明 沈栋林 CHANG Yuyin;LU Tailing;LU Ming;SHEN Donglin(Department of Pediatrics,the Affiliated Hospital of Xuzhou Medical University,Xuzhou,Jiangsu 221000,China;Department of Respiratory WardⅡ,Xuzhou Children’s Hospital,Xuzhou,Jiangsu 221000,China)
出处 《重庆医学》 2025年第8期1894-1898,1903,共6页 Chongqing Medical Journal
关键词 乳糖不耐受 婴幼儿 肠道菌群 短链脂肪酸 粪便 lactose intolerance infants gut microbiota short-chain fatty acids stool
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