Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice
Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice
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DOI：
10.1073/pnas.0601056103
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发表时间：
2006-08-15
影响因子：
11.1
通讯作者：
Nicholson, Jeremy K.
中科院分区：
文献类型：
--
作者：
Dumas, Marc-Emmanuel;Barton, Richard H.;Nicholson, Jeremy K.
在这里，我们研究肠道微生物群和宿主代谢表型之间的复杂关系，这些表型与饮食诱导的葡萄糖稳态受损和非酒精性脂肪性肝病（NAFLD）相关，已知对这些疾病特征易感的小鼠品系（129S6），使用血浆和尿液代谢分型，通过1H NMR波谱实现。光谱的多元统计模型显示，129S6小鼠葡萄糖稳态受损和NAFLD的遗传易感与胆碱代谢的破坏有关，即血浆磷脂酰胆碱循环水平低，尿中甲胺（二甲胺、三甲胺和三甲胺-氧化三甲胺）的高排泄，由共生肠道微生物群和哺乳动物酶系统共同处理。菌株129S6的微生物在高脂肪饮食中将胆碱转化为甲胺，降低了胆碱的生物利用度，并模仿胆碱缺乏饮食的影响，导致NAFLD。这些数据还表明，肠道微生物群可能在胰岛素抵抗的发展中发挥积极作用。
Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (129S6) known to be susceptible tothese disease traits, using plasma and urine metabotyping, achieved by 1H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-Noxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiotal in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.