Hamilton M Kristina, Boudry Gaëlle, Lemay Danielle G, Raybould Helen E
Department of Anatomy, Physiology and Cell Biology, University of California Davis School of Veterinary Medicine, Davis, California;
Institut National de la Recherche Agronomique (INRA) UR 1341 Alimentation and Adaptations Digestives, Nerveuses et Comportementales (ADNC), St.-Gilles, France.
Am J Physiol Gastrointest Liver Physiol. 2015 May 15;308(10):G840-51. doi: 10.1152/ajpgi.00029.2015. Epub 2015 Mar 6.
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.
肠道上皮的病理生理变化与肠道微生物群改变和肥胖症发病之间的因果关系已被提出，但尚未明确。本研究的目的是确定在啮齿动物高脂（HF）饮食诱导的肥胖中，小肠和大肠中肠道屏障功能受损与微生物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、体重和肥胖程度。使用异硫氰酸荧光素标记的葡聚糖（4000 Da，FD-4）和辣根过氧化物酶（HRP）探针在尤斯灌流小室中评估离体屏障功能、基因表达和肠道微生物群落。1周后，回肠的细胞旁通透性立即但可逆地增加，白细胞介素-10表达降低，梭菌纲内的属丰度降低。在大肠中，HF饮食喂养时，HRP通量和拟杆菌目内的属丰度随时间增加，并与体重增加和肥胖症的发病相关。数据显示，摄入HF饮食后回肠立即受到损伤，这种损伤迅速恢复，并先于大分子通过大肠上皮的增加。本研究有助于理解饮食诱导肥胖中的微生物失调和肠道病理生理学，并已确定回肠中的白细胞介素-10和颤螺菌属以及大肠中的跨细胞通量是肠道中可能导致肥胖和代谢紊乱的潜在早期损伤。
