Although the relationship between cholesterol, triglycerides, and cardiovascular disease is well established, little is known about the role of the third major class of lipids – phospholipids. In this regard, the intestinal microflora play a crucial role in that they digest and absorb many crucial nutrients, including lipids. Therefore in this study the authors attempted to discover whether a link exists between gut-flora-dependent phospholipid metabolism and atherosclerosis risk through generation of pro-atherosclerotic metabolites.
Three metabolites of the dietary lipid phosphatidylcholine — choline, trimethylamine N-oxide (TMAO) and betaine — were firstly identified from a clinical cohort prior to the onset of a clinical cardiovascular event. Subsequently, a mouse model was used where dietary supplementation with choline, TMAO or betaine was found to upregulate multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Lastly, studies using germ-free mice showed that suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis.
Gut flora play an important role in the production of metabolites that induce atherosclerosis. The results suggest that an appropriately targeted probiotic intervention may be of use in preventing cardiovascular disease.
- Wang Z, Klipfell E, Bennett BJ et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-65.
Metabolomics is the study of small-molecule metabolite profiles formed by cellular processes.