Preventing heart failure and managing diabetes are the potential benefits of a new discovery by University of Guelph researchers.   

The team has shown that nitrate – already a popular dietary supplement for athletes – can help improve cardiac health even in a state of obesity.  In an intriguing finding, the study is the first to link heart-health benefits of nitrate to gastrointestinal microbes.   

That points to a yet-unexplored “nitrate-gut-heart axis,” underlining the importance of gut health to overall health and well-being, said co-author Dr. Graham Holloway, a professor in the Department of Human Health and Nutritional Sciences (HHNS) within U of G’s College of Biological Science (CBS).  

The paper appears online in the journal Diabetes.   

In their study, the researchers fed mice a high-fat diet that causes obesity, along  with or without a nitrate supplement. They found that nitrate provided a strong cardioprotective effect in obese mice, lowering blood pressure and reducing the extent of changes to heart muscle.    

Testing a gut-heart connection  

Looking to explain this benefit, the team explored  away from the heart and toward the gut.   

Scientists already knew that intestinal bacteria are important in nitrate metabolism and that nitrate can change the gut microbiome, or the array of microorganisms in the gastrointestinal tract. The U of G researchers wondered whether the microbiome might be involved in cardioprotective effects – making a heart-gut connection.   

Using fecal microbial transfers from obese mice that received nitrate supplementation to mice without supplements led to improved cardiometabolic health. The tests also improved control of glucose metabolism, a factor in diabetes.   

The findings point to ways to help prevent heart failure and associated cardiovascular problems, said Holloway.   

He said the researchers don’t know how those GI effects are connected to heart health.   

Potential therapies for cardiovascular problems

Their work may ultimately lead to new dietary supplements or dietary recommendations for people at risk of heart failure, said Holloway.   

“Nitrate is in a lot of foods,” he said, pointing to spinach and beetroot that contain high amounts of the nutrient. “We might be able to prevent a lot of potential complications.”  

An expert in gut microbiome studies, Dr. Emma Allen-Vercoe, professor in CBS’s Department of Molecular and Cellular Biology, found nitrate increased amounts of specific bacteria, ultimately preventing changes in gut microbiota associated with disease.  

“Nitrate prevents detrimental effects of a high-fat diet on myocardial function,” said Allen-Vercoe. At U of G, she runs the “robo-gut” lab, which mimics the workings of the human GI tract including various gut microbes.   

Co-author Heather Petrick, a PhD candidate in Holloway’s lab, is now working with collaborators at the Maastricht University Medical Centre in the Netherlands. They aim to set up human clinical trials to learn more about possible gut-heart connections with nitrate. 

Dr. Jeremy Simpson, also a co-author, is a cardiovascular physiologist in HHNS. He said, “This work has significant implications for heart patients, particularly those with diabetes-related co-morbidities. This study suggests that therapeutic approaches aimed at improving glycemia and preventing cardiovascular disease should also focus on the gut microbiome and highlights the importance of the nitrate-gut-heart axis in the development of cardiac abnormalities.”

Holloway studies integrative physiology, including lifestyle implications for health. He said this new paper brings together interdisciplinary strengths in physiology, cardiovascular health and the gut microbiome.   

“This amalgamation of biologists is one of our strengths as a college and a university,” Holloway  said.    

Along with several U of G graduate students, the study also included collaborators from McMaster University and researchers in the Netherlands, Poland and Brazil.  

This study was funded by the Natural Sciences and Engineering Research Council.  


Dr. Graham Holloway