Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype.
Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype.
复制标题
DOI：
10.1371/journal.pone.0150943
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Garvey WT
中科院分区：
文献类型：
--
作者：
Zhang W;Hartmann R;Tun HM;Elson CO;Khafipour E;Garvey WT
在过去的十年中，新出现的证据将肠道微生物组成的改变与广泛的疾病联系起来，包括肥胖症，2型糖尿病和心血管疾病。Toll样受体（TLR）是肠道菌群与宿主先天免疫系统相互作用的主要介质，参与宿主肠道菌群的定位和构建。先前的一项研究发现，TLR5缺陷小鼠（TLR5KO1）改变了肠道微生物组成，导致代谢综合征的发展，包括高脂血症，高血压，胰岛素抵抗和肥胖增加。在本研究中，研究了第二种TLR5缺陷型小鼠模型（TLR5KO2）。与同窝对照组相比，TLR5缺陷型小鼠没有表现出与代谢综合征相关的代谢异常，该同窝对照组维持正常食物或喂食高脂肪饮食后。对同窝TLR5KO2和野生型小鼠的肠道微生物组成的分析显示，基因型之间的总体微生物群结构没有显著差异。然而，TLR5KO2微生物群与先前报道的患有代谢综合征的TLR5KO1小鼠的微生物群明显不同。我们的结论是，在给定的环境中，微生物群的组成改变可能导致代谢综合征，但这不是TLR5缺乏本身的结果。
Over the past decade, emerging evidence has linked alterations in the gut microbial composition to a wide range of diseases including obesity, type 2 diabetes, and cardiovascular disease. Toll-like receptors (TLRs) are the major mediators for the interactions between gut microbiota and host innate immune system, which is involved in the localization and structuring of host gut microbiota. A previous study found that TLR5 deficient mice (TLR5KO1) had altered gut microbial composition which led to the development of metabolic syndrome including hyperlipidemia, hypertension, insulin resistance and increased adiposity. In the current study, a second TLR5-deficient mouse model was studied (TLR5KO2). TLR5 deficient mice did not manifest metabolic abnormalities related to the metabolic syndrome compared with littermate controls maintained on normal chow or after feeding a high fat diet. Analysis of the gut microbial composition of littermate TLR5KO2 and wild type mice revealed no significant difference in the overall microbiota structure between genotypes. However, the TLR5KO2 microbiota was distinctly different from that previously reported for TLR5KO1 mice with metabolic syndrome. We conclude that an altered composition of the microbiota in a given environment can result in metabolic syndrome, but it is not a consequence of TLR5 deficiency per se.