Lipid Metabolism by Gut Microbes and Atherosclerosis

A recent metabolomic study provides evidence that microbial metabolism of lipids in the gut yields product(s) that promote atherosclerosis.These results add another dimension-the microbiome-to the complex determinants of atherogenesis.Atherosclerotic vascular disease is a complex pathophenotype that is governed by genetic and environmental determinants.The mechanistic interplay between specific genetic loci that predispose to atherosclerosis and promotive dietary factors is well known and serves as the basis for current preventive therapeutic strategies designed to limit expression of overt disease.For example, we routinely urge our patients at risk for atherosclerosis to reduce the intake of cholesterolrich foods and, for those who are glucose intolerant, to limit the intake of carbohydrates.These exhortations are predicated on the view that dietary risk factors are directly absorbed from the gut to exert their adverse vascular effects.What has been neglected until recently, however, is the role of commensal intestinal microorganisms in the metabolism of foodstuffs and their potential consequences for host metabolism and disease pathogenesis.A recent outcome of the application of contemporary genomics to human pathobiology is the ability to characterize the microbiome of these commensal organisms and to do so in conjunction with exploring the functional consequences of these unique microbiota for human biology and disease.Gut flora can significantly influence the bioavailability of dietary constituents and their metabolism in mammalian hosts. 1 Susceptibility to obesity 2 and insulin resistance 3 are determined by the specific metabolic characteristics of gut microbiota.The ability of this unique microbial community to exert such dramatic effects on metabolism should not be surprising when one considers that nearly 99% of the genes in humans are microbial in origin.4 With the rapid evolution of metagenomic technologies, the genetic variation in intestinal mi-E-mail jloscalzo@partners.org