An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice.
An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice.
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DOI：
10.1038/ismej.2012.153
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发表时间：
2013-04
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--
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中科院分区：
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脂多糖内毒素是唯一已知的细菌产物，当以其纯化形式皮下输注到小鼠中时，其可通过炎症介导的途径诱导肥胖和胰岛素抵抗。在这里，我们表明，一种产生内毒素的细菌分离自病态肥胖的人的肠道诱导肥胖和胰岛素抵抗的无菌小鼠。产生内毒素的肠杆菌的相对丰度从志愿者肠道细菌的35%下降到不可检测，在此期间，志愿者减掉了174.8 kg初始体重的51.4 kg，并在全谷物、中药食品和益生元饮食23周后从高血糖和高血压中恢复。志愿者肠道中内毒素生物合成基因丰度的降低与循环内毒素负荷的降低和炎症的减轻相关。无菌C57 BL/6 J小鼠与从志愿者肠道分离的阴沟肠杆菌B29菌株的单一结合在高脂肪饮食中诱导了完全发展的肥胖和胰岛素抵抗，但在正常饮食中没有，而在高脂肪饮食中的无菌对照小鼠没有表现出相同的疾病表型。Enteroclavin诱导的肥胖小鼠表现出血清内毒素负荷增加和炎症状况加重。这种人源性内毒素生产者在无菌小鼠中的肥胖诱导能力表明，它可能导致其人类宿主肥胖的发展。
Lipopolysaccharide endotoxin is the only known bacterial product which, when subcutaneously infused into mice in its purified form, can induce obesity and insulin resistance via an inflammation-mediated pathway. Here we show that one endotoxin-producing bacterium isolated from a morbidly obese human's gut induced obesity and insulin resistance in germfree mice. The endotoxin-producing Enterobacter decreased in relative abundance from 35% of the volunteer's gut bacteria to non-detectable, during which time the volunteer lost 51.4 kg of 174.8 kg initial weight and recovered from hyperglycemia and hypertension after 23 weeks on a diet of whole grains, traditional Chinese medicinal foods and prebiotics. A decreased abundance of endotoxin biosynthetic genes in the gut of the volunteer was correlated with a decreased circulating endotoxin load and alleviated inflammation. Mono-association of germfree C57BL/6J mice with strain Enterobacter cloacae B29 isolated from the volunteer's gut induced fully developed obesity and insulin resistance on a high-fat diet but not on normal chow diet, whereas the germfree control mice on a high-fat diet did not exhibit the same disease phenotypes. The Enterobacter-induced obese mice showed increased serum endotoxin load and aggravated inflammatory conditions. The obesity-inducing capacity of this human-derived endotoxin producer in gnotobiotic mice suggests that it may causatively contribute to the development of obesity in its human host.
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