Quaternary amine metabolism in gut microbiota

Quaternary amines such as choline and carnitine are essential nutrients for humans supplied from daily food; however, quaternary amines metabolism by gut microbiota can lead to the development of various diseases, including non-alcoholic fatty liver disease and cardiovascular disease. It is hypothesized that both diseases are promoted by microbial catabolism of choline and carnitine to trimethylamine (TMA). Proteus mirabilis is a Gram-negative gut proteobacterium, which can metabolize choline anaerobically to form TMA. I demonstrated that the identified cutC gene is essential for choline degradation and subsequent TMA production in this bacterium. Using P. mirabilis as the model, I investigated the physiological role of quaternary amine metabolism from the bacterial perspective and demonstrated that P. mirabilis can rapidly uptake and degrade choline to enhance growth rate, cell yield and swarming speed under anaerobic and microaerophilic conditions. I also provide the first evidence of a novel choline-metabolizing microcompartment, which is present in both vegetative and swarming cells supplemented with choline. Another important dietary source of TMA in human gut is carnitine. I used two model proteobacteria Acinetobacter baumannii and Escherichia coli in this project to investigate the role of carnitine metabolism to TMA in health and disease. A. baumannii and E. coli can use carnitine as a growth substrate to produce TMA. To better understand the role of quaternary amine metabolism in host health and disease, I used Caenorhabditis elegans model to investigate carnitine metabolism on the life span of the worm. My data suggest that malate, the degradation product of carnitine, extends the life span of C. elegans fed on A. baumannii or E. coli. Together, my study reveals that choline and carnitine metabolism as an adaptation strategy for gut proteobacteria and contributes to better understand the ecology of these TMA-forming gut bacteria in health and disease.