Gut microbiota and atherosclerosis: a bacterial perspective

Research in the past two decades has now convincingly demonstrated that humans are “super-organisms”. We coexist with trillions of microorganisms, collectively termed the microbiota. Our microbiota dramatically impact on our development, health and wellbeing. However, besides our understanding the potential of the microbiota to cause infections, our knowledge pertaining to human-centric functional contributions of this community is very limited.
This PhD project aims to explore a highly topical issue of how our diet is modified by microorganisms in the gut, affecting the health of the host organism. The PhD will focus on the bacterial production of trimethylamine in the human gut. Trimethylamine is absorbed from the gut and oxidized by the liver, the resultant molecule, trimethylamine oxide, promotes atherosclerotic plaque formation in blood vessels and consequently cardiovascular disease (Wang et al. 2011; Koeth et al., 2013). Trimethylamine production is primarily governed by oral and intestinal microbes, through degradation of dietary quaternary amines, such as choline and carnitine, both of which are also essential vitamins for human. Using molecular genetics, biochemistry and bioinformatics approaches, we have recently identified the carnitine-to-trimethylamine metabolic pathway exploited by gut microbiota, including commensal and pathogenic gut microbiota such as Escherichia coli(Zhu et al., 2014).
Several key questions remain. For example, what is the selective advantage to the gut microbiota to maintain the metabolic capacity to produce trimethylamine? Indeed, our comparative genome analyses predict that, in these microbiota, intra- and interspecies variation occurs in the capacity to produce trimethylamine, and that the associated gene clusters have been disseminated between unrelated bacteria through horizontal gene transfer. We hypothesize that beyond its impact on cardiovascular disease, carnitine metabolism contributes to wider bacterium–host interactions, and that this trait also offers as yet undefined evolutionary advantages to the bacterium.
This PhD project aims to understand the role of carnitine degradation by gut microbiota from a bacterial perspective. Such information will be invaluable in developing interventions aimed at reducing gut microbiota-mediated trimethylamine production and the burden of cardiovascular disease.