Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice
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DOI：
10.2337/db07-1403
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发表时间：
2008-06-01
期刊：
影响因子：
7.7
通讯作者：
Burcelin, Remy
中科院分区：
文献类型：
--
作者：
Cani, Patrice D.;Bibiloni, Rodrigo;Burcelin, Remy
目的：糖尿病和肥胖症以分子来源不明的低度炎症为特征。我们先前已经确定，首先，代谢性内毒素血症控制炎症张力、体重增加和糖尿病，其次，高脂饮食调节肠道微生物区系和血浆脂多糖(LPS)浓度，即代谢性内毒素血症。因此，肠道微生物区系的改变是否控制代谢性疾病的发生还有待论证。研究设计和方法-我们通过抗生素治疗改变肠道微生物区系，以证明肠道微生物区系的变化可能负责控制代谢性内毒素血症、低度炎症、肥胖和2型糖尿病，并提供一些相关机制。结果-我们发现抗生素治疗引起的肠道微生物区系的变化降低了高脂喂养和ob/ob小鼠的代谢内毒素血症和盲肠内毒素含量。这种作用与减少糖耐量、体重增加、脂肪块发展、降低炎症、氧化应激和内脏脂肪组织中巨噬细胞渗透标记基因的表达有关。重要的是，高脂肪喂养大大增加了肠道通透性，降低了紧密连接蛋白编码基因的表达。此外，ob/ob CD14(-/-)突变小鼠中CD14的缺失模拟了抗生素的代谢和炎症效应。结论-这一新发现表明，肠道微生物区系的变化通过增加肠道通透性的机制控制代谢性内毒素血症、炎症和相关疾病。因此，开发改变肠道微生物区系以控制肠道通透性、代谢性内毒素血症和相关疾病的策略将是有用的。
OBJECTIVE-Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases.RESEARCH DESIGN AND METHODS-We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect.RESULTS-We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-/-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics.CONCLUSIONS-This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.