Osborn Lucas J, Orabi Danny, Goudzari Maryam, Sangwan Naseer, Banerjee Rakhee, Brown Amanda L, Kadam Anagha, Gromovsky Anthony D, Linga Pranavi, Cresci Gail A M, Mak Tytus D, Willard Belinda B, Claesen Jan, Brown J Mark
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA.
Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195, USA.
Immunometabolism. 2021;3(4). doi: 10.20900/immunometab20210029. Epub 2021 Sep 18.
A major contributor to cardiometabolic disease is caloric excess, often a result of consuming low cost, high calorie fast food. Studies have demonstrated the pivotal role of gut microbes contributing to cardiovascular disease in a diet-dependent manner. Given the central contributions of diet and gut microbiota to cardiometabolic disease, we hypothesized that microbial metabolites originating after fast food consumption can elicit acute metabolic responses in the liver.
We gave conventionally raised mice or mice that had their microbiomes depleted with antibiotics a single oral gavage of a liquified fast food meal or liquified control rodent chow meal. After four hours, mice were sacrificed and we used untargeted metabolomics of portal and peripheral blood, 16S rRNA gene sequencing, targeted liver metabolomics, and host liver RNA sequencing to identify novel fast food-derived microbial metabolites and their acute effects on liver function.
Several candidate microbial metabolites were enriched in portal blood upon fast food feeding, and were essentially absent in antibiotic-treated mice. Strikingly, at four hours post-gavage, fast food consumption resulted in rapid reorganization of the gut microbial community and drastically altered hepatic gene expression. Importantly, diet-driven reshaping of the microbiome and liver transcriptome was dependent on an intact microbial community and not observed in antibiotic ablated animals.
Collectively, these data suggest a single fast food meal is sufficient to reshape the gut microbial community in mice, yielding a unique signature of food-derived microbial metabolites. Future studies are in progress to determine the contribution of select metabolites to cardiometabolic disease progression and the translational relevance of these animal studies.
热量摄入过多是导致心脏代谢疾病的一个主要因素，这通常是食用低成本、高热量快餐的结果。研究表明，肠道微生物群以饮食依赖的方式在心血管疾病中发挥关键作用。鉴于饮食和肠道微生物群对心脏代谢疾病的核心作用，我们推测快餐消费后产生的微生物代谢产物可在肝脏中引发急性代谢反应。
我们给常规饲养的小鼠或用抗生素清除微生物群的小鼠单次经口灌胃一顿液化快餐或液化对照啮齿动物饲料。4小时后，处死小鼠，我们使用门静脉血和外周血的非靶向代谢组学、16S rRNA基因测序、靶向肝脏代谢组学以及宿主肝脏RNA测序来鉴定新型快餐衍生的微生物代谢产物及其对肝功能的急性影响。
喂食快餐后，几种候选微生物代谢产物在门静脉血中富集，而在抗生素处理的小鼠中基本不存在。引人注目的是，灌胃后4小时，食用快餐导致肠道微生物群落迅速重组，并极大地改变了肝脏基因表达。重要的是，饮食驱动的微生物群和肝脏转录组重塑依赖于完整的微生物群落，在抗生素清除微生物的动物中未观察到这种现象。
总体而言，这些数据表明一顿快餐就足以重塑小鼠的肠道微生物群落，产生独特的食物衍生微生物代谢产物特征。目前正在进行进一步研究，以确定特定代谢产物对心脏代谢疾病进展的影响以及这些动物研究的转化相关性。
