L-carnitine, which has long been present in large quantities in red meat (such as beef and lamb), was once considered a nutrient along with choline and lecithin, but a study in the United States two years ago pointed out that L-carnitine may change from beneficial to harmful under the action of intestinal bacteria, leading to atherosclerosis. Not long ago, a scientist proposed a new idea to prevent heart disease by interfering with intestinal bacteria based on this finding. The reason why L-carnitine and choline, which were considered as nutrients in the past and even once recognized as food fortification by various countries, can induce atherosclerosis is that these substances can be metabolized by bacteria in the large intestine to produce trimethylamine, which is absorbed by the intestine and metabolized in the liver to trimethylamine-N-oxide (TMAO), which can promote atherosclerosis. The study found that the same amount of trimethylamine was consumed in the liver. It has been found that omnivores can produce more TMAO than vegetarians when consuming the same amount of L-carnitine because of the specific type of bacteria in the intestine of omnivores. It was found that feeding L-carnitine to mice for a long period of time could change the composition of bacteria in the animals’ intestines, leading to elevated TMAO in the blood and atherosclerosis. These changes do not occur if the growth of bacteria is inhibited. Intestinal bacteria are responsible for atherosclerosis induced by red meat consumption. An epidemiological survey of 2595 individuals found no direct relationship between plasma levels of L-carnitine and the incidence of cardiovascular disease and serious cardiovascular outcomes. However, if TMAO was also elevated in the blood, there was a correlation between the level of L-carnitine and the incidence of cardiovascular disease and the occurrence of serious cardiovascular outcomes. Until the key role of gut bacteria was discovered, the underlying causes were not understood. Since gut bacteria are a contributor to TMAO production, can the prevention of heart disease be achieved by interfering with microbial metabolism through drugs to reduce TMAO production?On December 17, 2015, the journal Cell (CELL) published a study conducted by Cleveland Medical Center that, for the first time, used drugs that interfere with the metabolic activity of gut bacteria and proposed a new strategy to treat heart disease by regulating the gut flora The journal CELL published a study conducted at Cleveland Medical Center that used drugs that interfere with the metabolic activity of intestinal bacteria for the first time, suggesting a new strategy for treating heart disease by regulating intestinal flora. Previously, the main way to target this pathway was to inhibit the enzyme that converts trimethylamine in the liver. However, this approach has caused liver damage and trimethylamine accumulation. Hazen and his team, corresponding authors of the latest paper in Cell, have found a more promising way to stop trimethylamine formation at its source by directly targeting intestinal bacteria. Hazen and Zeneng Wang, the paper’s first author, screened for the compound 3,3-dimethylbutanol DMB (3,3-dimethyl-1-butanol), which inhibits trimethylamine production. The researchers established a mouse model of atherosclerosis and provided it with a diet rich in choline. The study showed that DMB treatment significantly reduced TMAO levels and inhibited plaque formation in the mice, with no toxic side effects. Further studies showed that DMB does work by inhibiting the formation of trimethylamine. And DMB does not kill gut bacteria, but only reduces the percentage of specific bacteria in the gut that are associated with high levels of trimethylamine, TMAO and atherosclerosis. “The drug works very well by not killing the bacteria but blocking the pathway,” Hazen said. “Compared to antibiotics, non-lethal drugs face less selection pressure and are less likely to trigger resistance.” DMB therapy differs from cholesterol-lowering drugs, such as Lipitor, in that it targets molecular pathways in intestinal bacteria rather than metabolic enzymes in human cells. “This could become a completely new therapeutic strategy for the treatment of cardiovascular and metabolic diseases.” The Mediterranean-style diet is based on fish, legumes, vegetables, fruits, nuts and olive oil, with moderate amounts of red wine. This diet combination has been particularly popular in recent years and is thought to prevent cardiovascular disease. This Cleveland Medical Center study found that the Mediterranean-style diet exerts its health effects by altering the activity of intestinal bacteria. Dietary supplementation with a form of DMB, which is abundant in red wine and olive oil, prevented mice from converting unhealthy foods into artery-clogging metabolic byproducts. For most people, a Mediterranean-style diet to slow down heart disease and other health problems is an immediately viable idea.