A New Study Links Gut Bacteria to Cardiovascular Disease Risk

They say “you are what you eat.” But, like many things in life, the truth is a little more complicated than a bumper sticker slogan. According to new research lead by Dr. Na Fei published in the journal PLOS ONE, what our gut bacteria do with the food we eat can impact our risk of cardiovascular disease.

Cardiovascular Disease — A Global Threat to Health

Dr. Fei’s research is part of an ongoing prospective cohort study that started in 2009 called Modeling the Epidemiologic Transition Study (METS). Over 2500 people of African descent are enrolled in the parent study. The objective of the study overall is to investigate the association between body composition, physical activity and cardiovascular disease risk in five geographically diverse populations. Cardiovascular disease can include heart disease, heart attack, stoke, heart failure and other heart conditions.

Prospective cohort study = a research study where researchers follow groups of individuals over time to watch for outcomes, such as the development of a disease. Cohorts of people in these studies are alike in many ways but differ by a certain characteristic that they can be compared based on for a particular outcome.

The PLOS ONE study, headed by research teams at the University of Chicago and Loyola University Chicago, examined the gut and oral bacterial populations (microbes in the gut and mouth) in over 600 people of African-origin from several countries. The hypothesis was that changes in the population of bacteria that populate the human digestive system leads to biological changes that predispose people to cardiovascular disease.

Microbiomes and Cardiometabolic Disease

Bacteria live naturally in many areas of the body and are referred to collectively as “microbiomes”. Two of the most well studied and easily accessible bacterial populations are the oral microbiome (studied through saliva samples) and the gut microbiome (studied through fecal samples). The researchers of the new PLOS ONE study speculated that changes in these microbiomes change the risk of developing a condition called Cardiometabolic Disease (CMD), also known as Cardiometabolic Syndrome.

CMD is associated with five changes in the body that increase the risk of cardiovascular disease:

• Obesity
• High blood glucose (high blood sugar)
• High blood pressure
• Decreased high density lipoprotein (the ‘good’ cholesterol)
• High levels of triglycerides

While diet and exercise habits contribute to these changes, emerging evidence suggests that the microbiome could play a significant role in the development of the biological changes associated with CMD. In other words, the specific microbes that live in your gut may put you at risk or protect you from obesity and other risk factors for cardiovascular disease.

Research done as part of the METS program is focused on people of African-origin because this cohort represents one of the fastest growing groups for cardiometabolic disease.

The Study – Microbiome Diversity and Cardiovascular Risk

Dr. Fei and colleagues collected fecal samples from 655 men and women from Ghana, South Africa, Jamaica and the United States. Additionally, 620 of these subjects provided oral bacterial samples. Researchers identified and quantified the bacterial populations and then correlated them with, or looked at their relationship to, the five risk factors for CMD. People in the study who had three or more risk factors were considered to be at high risk for CMD, while people with two or fewer risk factors was classified as low risk.

The results? Researchers found that a decrease in the diversity of the gut microbiome was linked to an increase in a number of risk factors for CMD.

Diversity in the microbiome refers to the amount of different types of bacteria present – usually the more different types, the better. Diversity in the microbiome also refers sometimes to how evenly balanced these different types of bacteria are. Lowered diversity is common in elderly people, as well as people with autoimmune disease or obesity. Some relationships between the diversity of the gut microbiome and specific risk factors varied by country. For example, a lower gut microbiome diversity was associated with higher blood pressure in the African countries but not in people from Jamaica or the U.S.

Dr. Fei and colleagues also discovered that the specific types of bacteria found in the gut may impact the development of specific CMD risk factors. When participants had unusually high populations of Lachnospiraceae and Bacteroides in their gut, their risk for CMD increased. Unusually high levels of Clostridiaceae, Peptostreptococcaceae and Prevotella were linked to a lower risk.

Sidebar: Types of bacteria including Ruminococcaceae, Clostridiaceae, Peptostreptococcaceae and Prevotella, found in the PLOS ONE study to be associated with a lower risk of cardiometabolic disease, help to break down fat, complex carbohydrates and plant compounds in your gut. There is still a lot we have left to learn about how diet is linked to gut microbe population changes that predispose or protect against disease. But eating more fruits and vegetables (sources of plant nutrients and fiber that feeds healthy gut microbes), legumes and whole grains is a safe bet to protect yourself from heart disease and diabetes! Also, exercise has been linked with increases in some of these bacteria in the gut (at least in mice)!

Inflaming the Situation

How do gut bacteria alter CMD risk factors?

When Fei and colleagues looked at the genetic makeup of the gut bacteria, they found that types of bacteria associated with a higher CMD risk had certain profiles of metabolic genes. (Metabolic genes are pieces of DNA that direct the bacterium’s inner machinery to create products that play a role in metabolism, such as breaking down toxins or antibiotics, processing nutrients and more.) Specifically, the researchers found that bacteria enriched with genes for the production of lipopolysaccharides (LPS) were more common in patients with high cardiometabolic disease risk.

LPS help bacteria to maintain their structural integrity. They also protect bacteria from chemical attack. But if LPS enter the bloodstream, an inflammatory immune response is triggered. People with high levels of LPS in their bloodstream tend to develop obesity and insulin resistance, a risk factor for diabetes.

High levels of inflammation stemming from the gut microbiome have been implicated in many metabolic diseases. Additionally, chronic immune activity as a result of high levels of LPS can damage a number of organs in the body including the cardiovascular system, leading to an increased risk of cardiovascular disease.

Sex – The Missing Link

Women are notoriously under-represented in research in general and clinical research in particular. The inclusion of a significant female cohort (60% of the subjects were female) in this PLOS ONE study offered the potential to provide insight into sex differences in the gut microbiome and CMD risk. Unfortunately, the results were not separated by sex, preventing comparisons between the sexes. It is possible that once additional data are collected as part of the larger METS program, a sex-based assessment will be possible. This may be especially interesting in this cohort, as a recent review paper has suggested sex-dependent differences in the gut microbiome may cause differences in blood pressure due to diet and inflammation.

Tailor-Made Therapies

Previous studies have shown that gut microbiota differ in people across different regions and ethnic groups of the world. Whether these differences in bacterial profiles impact cardiometabolic disease risk is unknown.

This latest research suggests that a gut microbiome that lacks diversity or that contains unusually high levels of certain harmful types of bacteria may be a therapeutic target for the treatment of CMD. But the finding that different types of bacteria increase the risk differently in different populations of people suggests that a geographically or ethnically tailored approach would be most effective.

This blog post also includes contributions from LIFE Apps bloggers Kate Secombe and Paige Jarreau.