Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent
Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent
复制标题
高脂饮食喂养的大鼠肠道屏障功能和肠道微生物群的变化是动态的且具有区域依赖性
DOI：
10.1152/ajpgi.00029.2015
复制
发表时间：
2015-05-15
影响因子：
4.5
通讯作者：
Raybould, Helen E.
中科院分区：
文献类型：
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作者：
Hamilton, M. Kristina;Boudry, Galle;Raybould, Helen E.
肠道上皮的病理生理学变化和肠道微生物群的改变与肥胖症的发生之间存在因果关系，但尚未确定。本研究的目的是确定啮齿类动物高脂饮食诱导的肥胖中小肠和大肠中肠屏障功能受损与微生物生态失调之间的时间关系。给大鼠喂食HF饮食（45%脂肪）或正常食物（C，10%脂肪）1、3或6周;测量食物摄入量、体重和肥胖。使用FITC标记的葡聚糖（4，000 Da，FD-4）和辣根过氧化物酶（HRP）探针在Ussing室中离体评估屏障功能、基因表达和肠道微生物群落。1周后，回肠中细胞旁通透性立即但可逆地增加，IL-10表达减少，梭菌纲内属的丰度减少。在大肠中，类杆菌目内的属的HRP通量和丰度随HF饮食的时间而增加，并与体重增加和肥胖的发病相关。数据显示，响应于摄入HF饮食，回肠中的立即损伤迅速恢复，并且在大分子穿过大肠上皮增加之前。这项研究提供了对饮食诱导的肥胖症中微生物群失调和肠道病理生理学的了解，并确定了回肠中的IL-10和颤螺旋菌以及大肠中的跨细胞流动是肠道潜在的早期损伤，可能导致肥胖和代谢紊乱。
A causal relationship between the pathophysiological changes in the gut epithelium and altered gut microbiota with the onset of obesity have been suggested but not defined. The aim of this study was to determine the temporal relationship between impaired intestinal barrier function and microbial dysbiosis in the small and large intestine in rodent high-fat (HF) diet-induced obesity. Rats were fed HF diet (45% fat) or normal chow (C, 10% fat) for 1, 3, or 6 wk; food intake, body weight, and adiposity were measured. Barrier function ex vivo using FITC-labeled dextran (4,000 Da, FD-4) and horseradish peroxidase (HRP) probes in Ussing chambers, gene expression, and gut microbial communities was assessed. After 1 wk, there was an immediate but reversible increase in paracellular permeability, decrease in IL-10 expression, and decrease in abundance of genera within the class Clostridia in the ileum. In the large intestine, HRP flux and abundance of genera within the order Bacteroidales increased with time on the HF diet and correlated with the onset of increased body weight and adiposity. The data show immediate insults in the ileum in response to ingestion of a HF diet, which were rapidly restored and preceded increased passage of large molecules across the large intestinal epithelium. This study provides an understanding of microbiota dysbiosis and gut pathophysiology in diet-induced obesity and has identified IL-10 and Oscillospira in the ileum and transcellular flux in the large intestine as potential early impairments in the gut that might lead to obesity and metabolic disorders.