Zhang Wei, Hartmann Riley, Tun Hein Min, Elson Charles O, Khafipour Ehsan, Garvey W Timothy
Department of Nutrition Sciences, School of Health Professions, the University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada.
PLoS One. 2016 Mar 7;11(3):e0150943. doi: 10.1371/journal.pone.0150943. eCollection 2016.
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.
在过去十年中，新出现的证据表明肠道微生物组成的改变与多种疾病有关，包括肥胖症、2型糖尿病和心血管疾病。Toll样受体（TLRs）是肠道微生物群与宿主固有免疫系统相互作用的主要介质，而宿主固有免疫系统参与宿主肠道微生物群的定位和结构形成。先前的一项研究发现，Toll样受体5缺陷小鼠（TLR5KO1）的肠道微生物组成发生了改变，这导致了代谢综合征的发展，包括高脂血症、高血压、胰岛素抵抗和肥胖增加。在当前的研究中，对第二种Toll样受体5缺陷小鼠模型（TLR5KO2）进行了研究。与以正常食物喂养的同窝对照小鼠或喂食高脂饮食后的同窝对照小鼠相比，Toll样受体5缺陷小鼠未表现出与代谢综合征相关的代谢异常。对同窝TLR5KO2小鼠和野生型小鼠的肠道微生物组成进行分析后发现，不同基因型之间的整体微生物群结构没有显著差异。然而，TLR5KO2小鼠的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。我们得出结论，在特定环境中微生物群组成的改变可导致代谢综合征，但这并非Toll样受体5缺陷本身所导致的结果。
