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Behind the bench... with Dr. Stanley Hazen, Cleveland Clinic and Lerner Research Institute

Gary H. Gibbons, M.D. - April 25, 2013

man in a lab coat that says "Cleveland Clinic"

We have known for decades that there is a strong link between the foods we eat and our risk of developing cardiovascular disease (CVD). Studies have taught us about the value of "heart-healthy" foods contained in the DASH and "Mediterranean-style" diets, which are rich in fruits, vegetables, whole grains, fish and "good fats" such as olive oil. Nevertheless, controversies persist about the potential deleterious effects of high red meat consumption. Scientists still don't know why certain foods reduce the risk of CVD and others don't.

Recently, a provocative series of NHLBI-funded research studies have provided some important new insights into the potential link between red meat consumption and the "clogging of the arteries" that characterizes atherosclerotic CVD. According to Dr. Stanley Hazen and his colleagues at the Cleveland Clinic and Lerner Research Institute, the main culprit behind heart disease associated with high red meat consumption may not be the saturated fat, but may instead be tied to our gut—specifically, gut bacteria's metabolism of L-carnitine, a substance found in red meat and energy drinks. This interaction between our diet and microbes residing in our gut leads to the production of TMAO, a pro-atherogenic substance that circulates in the blood and promotes the "clogging of arteries" by inhibiting the export of cholesterol from the atherosclerotic plaque. Dr. Hazen's groundbreaking work was published recently in Nature Medicine.

Dr. Hazen spoke with me in a candid, in-depth conversation about his recent contributions to science and what it may mean for the health of the nation and the future research opportunities that lie ahead.

"Behind the Bench" interview segments with Dr. Stanley Hazen:

Dr. Hazen's study and the findings of others are provocative in advancing our understanding of how the trillions of microbes that coexist in and around our bodies contribute to both health and disease. There is a fascinating interplay in which our dietary patterns influence the mix of microbes that reside in our gut; and in turn the particular mix of microbes in the gut influences how we digest and metabolize the food we eat. The chemical metabolites generated by our gut microbes are able to influence our body's immune system and thereby influence our response to allergens in our environment as well as the development of chronic diseases such as CVD. A striking finding of this study was the profound difference between the mix of gut microbes in vegans/vegetarians versus omnivores and the profound effect these dietary patterns have on the production of the microbe metabolite that promotes atherosclerotic CVD.

These findings suggest potentially exciting opportunities ahead for the development of novel blood tests that go beyond the measurement of cholesterol. This "biomarker" could enable a doctor to assess how a patient's diet and the personal mix of gut microbes influences the individual’s risk of CVD and result in a "personalized" modification of their treatment plan. In addition, it is interesting to speculate how the study of the chemicals generated by gut microbes may offer clues that guide the development of new drugs capable of mimicking the beneficial effects of "heart-healthy" foods.

Dr. Hazen's research studies are also notable for a "ping-pong" experimental approach that iteratively incorporated clinical work and studies in mice as well as large-scale population science and smaller-scale human studies. This work highlights the value of a cross-disciplinary approach to addressing an important question in discovery science that may have profound implications for enhancing human health. His research also advances our understanding of the dynamic interplay between the factors that predispose patients to CVD—our genetic inheritance, lifestyle choices and the environment in which we live (including the microbes that co-habit that environment with us!).

Dr. Hazen's work serves as a wonderful example of a NIH-funded clinician-scientist seeking to ask and answer critically important questions that are intended to enable his patients to live longer, healthier lives.



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