Study Finds Link Between Gut Bacteria and Obesity

Cleveland Clinic doctors discover other health risks associated with TMAO, including insulin resistance-a precursor to type 2 diabetes.

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Cleveland Clinic researchers continue to unlock more secrets about a common chemical byproduct produced by gut bacteria during the digestion of the nutrients choline, lecithin and carnitine.Those nutrients are found primarily in animal prducts, such as red meat, processed meats, egg yolks, and liver. The chemical byproduct is trimethylamine oxide (TMAO). TMAO is associated with injury to the arteries and reduced cardiovascular health.

During the past few years, Cleveland Clinic researchers, including J. Mark Brown, PhD, and Stanley Hazen, MD, PhD, have been studying TMAO’s effect on human health. Dr. Hazen found that high levels of TMAO are associated with a higher risk of severe cardiovascular events, such as stroke and heart attack.

In a separate study, published recently in the journal Cell Reports, Dr. Brown’s team found that high levels of TMAO are associated with higher incidence of type 2 diabetes. The research also found that blocking an enzyme that converts TMAO into its active form can help prevent obesity and insulin resistance, a condition in which the body no longer responds properly to the hormone insulin. Insulin helps the body use glucose (sugar) for energy or store glucose for future use. People with insulin resistance have too much glucose in their blood stream. When glucose levels get too high, the result is type 2 diabetes.

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Researchers hope that the better they understand the human body’s microbiome, the better able they will be to prevent disease or develop medications that can target potentially unhealthy activity, such as the formation of TMAO. Our microbiome is the collection of bacteria and other microorganisms that help break down food, protect us from disease, and perform other functions.

“Obesity, diabetes and cardiovascular disease are strongly linked,” Dr. Brown says. “While the microbiome has been shown to affect cardiovascular disease, there is as yet no concrete evidence of precisely how gut bacteria influence obesity. These findings shed light on a possible way to manipulate the microbiome with therapeutics to combat our obesity and diabetes epidemic.”

Predicting Health Problems

While researchers investigate ways to target the microbiome with new medications, doctors see some potential in using TMAO levels to help predict a person’s risk of future cardiovascular events. Dr. Hazen invented a test for TMAO. If high levels are detected, it could be a signal that a person could at least alter his or her diet to reduce those levels. This would mean less red and processed meat, as well as less full-fat dairy products and egg yolks. These changes are part of a heart-healthy diet anyway, so it’s good advice whether your TMAO levels are high or not.

Down the road, there may be even more effective ways than dietary changes to reduce your microbiome’s threat to your heart health.

“Given the numerous strong associations of the gut microbe-driven TMAO pathway with human disease, this work has broad implications for drug discovery efforts targeting gut microbes themselves,” says Dr. Hazen, chairman of the Department of Cellular & Molecular Medicine for the Lerner Research Institute and co-section head of Preventive Cardiology & Rehabilitation at Cleveland Clinic.

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