Fighting atherogenic TMAO with food and probiotics

该项目旨在确定可以降低三甲胺氧化（TMAO）水平的饮食成分，TMAO会导致动脉粥样硬化，并与几种死亡原因（如心力衰竭）以及糖尿病、阿尔茨海默氏症和慢性肾脏疾病等疾病密切相关。TMAO是由TMA在肝脏中形成的，TMA是由人类肠道中的某些细菌从饮食化合物如胆碱和肉碱中产生的。目前还没有有效的、可持续的降低氧化三甲胺水平的治疗方法。我们最近的研究提供了初步证据，证明多酚和膳食纤维可以减少TMA/TMAO的产生。另一种减少肠道TMA产生的合理策略是使用益生菌来改变微生物群的结构和功能，使其达到低TMA产生的表型（例如，通过竞争性排除产生TMA的微生物）。该项目旨在(i)使用NGS/生物信息学和qPCR方法识别区分低和高TMAO个体的肠道微生物群特征，以表征微生物群的结构和功能，并将其与TMAO表型联系起来；（ii）筛选多酚、纤维、益生菌和组合，以确定使用体外结肠模型减少TMA产生的高效治疗方法；（iii）确定有效治疗的作用模式。

This project seeks to identify dietary components that can decrease the levels of trimethylamine-Noxide (TMAO) which causes atherosclerosis and is strongly associated with several causes of death (e.g. heart failure) and with diseases such as diabetes, Alzheimer's and chronic kidney disease. TMAO is formed in the liver from TMA that is produced exclusively by certain bacteria in the human gut from dietary compounds such as choline and carnitine. There is no effective, sustainable treatment for reducing TMAO levels. Our recent research has provided preliminary evidence that polyphenols and dietary fibre can reduce production of TMA/TMAO. Another plausible strategy for reducing TMA production in the gut is to use probiotics to alter the structure and function of the microbiota towards a low TMA production phenotype (e.g. by competitive exclusion of microbes that produce TMA). This project seeks to (i) identify signatures of the gut microbiota that distinguish low and high TMAO individuals using NGS/bioinformatics and qPCR methods to characterise the structure and function of the microbiota and relate this with TMAO phenotype, (ii) screen polyphenols, fibres, probiotics and combinations to identify a highly effective treatment for reducing TMA production using an in vitro colon model, and (iii) determine the mode of action of the effective treatment.