A microbial byproduct of intestinal¹（肠道的） bacteria contributes to heart disease and serves as an accurate screening tool for predicting future risks of heart attack, stroke and death in persons not otherwise identified by traditional risk factors and blood tests, according to Cleveland Clinic research published today in The New England Journal of Medicine. The research team was led by Stanley Hazen, M.D., Ph.D., Vice² Chair of Translational Research, Chair of the Department of Cellular³ and Molecular⁴ Medicine for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation⁵ in the Miller⁶ Family Heart and Vascular⁷ Institute at Cleveland Clinic, and W.H. Wilson Tang, M.D., Department of Cardiovascular Medicine in the Miller Family Heart and Vascular Institute and Lerner Research Institute.

 

The current study is an extension of Dr. Hazen's previous work, in which he found that a chemical byproduct called trimethylamine（三甲胺） N-oxide (TMAO) is produced when intestinal bacteria digest the nutrient⁸ phosphatidylcholine, commonly known as lecithin（卵磷脂）. The prior research showed that TMAO levels in the blood were associated with heart disease. Dr. Hazen and colleagues have now confirmed that gut⁹ flora¹⁰ are essential in forming TMAO in humans and demonstrated a relationship between TMAO levels and future cardiac events like heart attack, stroke, and death -- even in those with no prior evidence of cardiac disease risk.

 

To demonstrate the role of gut flora in forming TMAO, human subjects were asked to eat two hard-boiled eggs (a common dietary source of lecithin) and a capsule of labeled lecithin (as a tracer). After ingestion, TMAO levels in the blood increased. However, when these same subjects were given a brief course of broad-spectrum antibiotics¹¹ to suppress their gut flora, their TMAO levels were suppressed, and no additional TMAO was formed, even after ingesting lecithin. These results demonstrated that the intestinal bacteria are essential for the formation of TMAO.

 

In the second phase of the study, the researchers measured TMAO levels in a large, independent, clinical cohort -- consisting of more than 4,000 adults undergoing cardiac evaluation¹² at Cleveland Clinic -- over a three-year follow-up period. They found that higher TMAO blood levels were associated with higher future risks of death and nonfatal heart attack or stroke over the ensuing three-year period, independent of other risk factors and blood test results. These results complement¹³ those of another recent study of Dr. Hazen's linking gut flora metabolism¹⁴ of a structurally¹⁵ similar nutrient found in animal products, carnitine, to TMAO production and heart attack risk.

 

"Heart disease remains¹⁶ the No. 1 killer¹⁷, and while we know how to reduce cholesterol¹⁸（胆固醇）, treat blood pressure, and reduce cardiac risks through diet and other interventions¹⁹, a substantial residual²⁰ risk still remains," Dr. Hazen said. "We need to find new pathways to attack heart disease, and these findings strongly suggest that further research into the involvement of gut microbiome in the development of cardiovascular disease could lead to new avenues of prevention and treatment of heart disease."

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