Effects of trimethylamine N-oxide on the growth and metabolism of gut bacteria

Trimethylamine N-oxide (TMAO) is an osmolyte that enters the bloodstream directly through consumption of fish, or through microbial metabolism of it and other dietary methylamines such as carnitine and choline, producing trimethylamine (TMA). TMA produced by microbes enters the blood and is transported to the liver, where it is converted back to TMAO by flavin-containing monooxygenases before being excreted in the urine. TMAO has been shown to potentially have beneficial effects on metabolic health and the gut-brain axis at normal physiological levels, while elevated serum levels are associated with cardiometabolic disease in Western patients. Bacteria in the family Enterobacteriaceae exhibit changes in their growth and metabolome in the presence of TMAO but why this occurs is not known. Growth experiments show that a caecal isolate of Klebsiella pneumoniae, a member of the Enterobacteriaceae, experience a more rapid growth rate, when grown anaerobically in the presence of TMAO, but may require oxygen to be present to produce TMA. K. pneumoniae will be subjected to differing concentrations of TMAO and oxygen to examine the effects on the metabolites produced, the genes expressed, and the rate of growth. This will be done by analysing spent media using GC-MS, qPCR targeting genes involved in anaerobic respiration, and measuring the turbidity of cultures over time. By understanding how bacteria in the gut interact with TMAO new insights can be gained as to how gut bacteria and their metabolites influence human health.