Fighting atherogenic TMAO with food and probiotics

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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.