Research News

As our knowledge evolves of how bacteria in our gut influence key organs like our heart, we caught up with W.H. Wilson Tang, MD, who studies these complex and still largely unknown connections. Dr. Tang, a cardiologist who is a principal investigator on several recent Cleveland Clinic-led human studies examining the connections between bacterial metabolites and cardiovascular disease, shared what we know and how further research will translate this knowledge to patient care.

What are metabolites and why are they important to study in research?

Dr. Tang says the study of metabolites — small molecules that are produced when the body breaks down food, drugs, chemicals or its own tissue — is a unique window into the symbiotic relationship between our environment and our body’s intricate processes.

“Over the last decade we’ve realized that while genetics may be the building code for our bodies, metabolites are the building blocks,” Dr. Tang explains. “The presence and levels of certain metabolites are manifestations of how our cells and organs are functioning and the influence of the outside environment.”

How does the digestive system work with the cardiovascular system?

Any cell in the body that requires nutrients and oxygen can be affected by microbes in the gut microbiome. Dr. Tang explains that microbial metabolites affect everyday function and resiliency of organs like the heart, like hormones and other endocrine systems.

“This comes into play in my clinical practice where I see patients with heart failure,” Dr. Tang says. “We know that harmful metabolites can influence the heart so it can’t meet the everyday needs of the organs. I want to be able to zoom down to the cellular and microbial level to try to fix this issue at the root cause, since we know that a lot of these harmful metabolites originate in the gut microbiome and are cleared by the liver and kidneys, which can be directly or indirectly impacted by the failing heart. How exactly gut microbes affect the heart is something my lab is still investigating.”

How does metabolite research translate to patient care?

Next steps on translating metabolic research into practical recommendations for patients include:

Conducting more studies to show cause and effect

“The challenge for a lot of researchers is that cause and effect can be very difficult to prove – we often don’t know whether we’re seeing a cause or consequence of the problem,” Dr. Tang explains. “It’s best to view what you measure in the blood as the first clue, but not definitive.”

Erythritol studies Dr. Tang conducted in close collaboration with the lab of Stan Hazen, MD, PhD were designed to demonstrate how what we consume affects our body. Examining platelets and biomarkers after participants consumed erythritol or sugar allowed the team to make informed recommendations to their patients.

Refining and developing tools for metabolite measurement

By developing and validating more sophisticated technology to measure the microbes in bloodwork, researchers and physicians can better determine the function of metabolites rather than just their composition. This data is essential, Dr. Tang explains, to quantify how choices we make in our everyday lives – e.g. what we eat, how much we move – affect conditions like heart failure, diabetes and kidney function.  

Prioritizing study of physiology and food science

Dr. Tang said food science needs to continue to advance for the medical community to properly assess and understand the world of metabolites. Since every individual’s microbial composition and function is unique, their physiologic responses to the same dietary nutrients can be vastly different. While the majority of investigators still focus on the healthiest foods to consume, there are limited insights into how an individual’s gut microbes will respond to these ingested foods, as well the biological effects of exercise.  Dr. Tang’s team is actively investigating how metabolites that are accumulating in patients with heart failure and kidney dysfunction can exert downstream biological effects.

“It’s critical that we start focusing on quantifying physiology and investigating concrete answers to the ways our choices in our daily life affect our health. We have historically paid very little attention to this as clinicians,” Dr Tang says.  “It may not be as simple as what kinds of food we eat, but how and when we eat them, as well as how much we are consuming.”

What has research shown us so far about how to ensure a healthy heart through your gut?

“The most common problems that lead to heart failure are high blood pressure, high cholesterol and diabetes,” Dr. Tang says. “There’s a saying in my field that if we control these three risk factors well, inflammation will come down and everybody’s hearts will be in good shape. Genetics obviously play a role in these conditions, but I often tell my patients that ‘nurture rises over nature.’”  

Although many people know eating “better” or exercises can protect their heart health, Dr. Tang emphasized the importance of further scientific discovery to direct these changes. He pointed to the Cleveland Clinic’s series of studies on TMAO, a metabolite formed when gut bacteria digest certain nutrients abundant in red meat and other animal products. Those findings showed TMAO is associated with heart disease, but Dr. Tang says the data also showed why even just limiting red meat consumption can be helpful for some people.

“Science has shown it’s not a one-size-fits-all approach – by continuing to investigate and develop more ways to show objectively how these changes are affecting our bodies, we can improve the recommendations we’re making to patients and build confidence with our patients that what they’re doing is protecting their health in the future,” he says.