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Disease and treatment

Statins improve the bacterial gut ecosystem of obese people

International research with solid input from Denmark shows that obese people who take statins have both lower levels of dangerous cholesterol in their blood and a healthier composition of gut bacteria.

Researchers have known for some time that being obese is clearly associated with an imbalance in the composition and functions of gut bacteria.

Researchers have also been interested in determining how to correct this imbalance, since it can be linked to the development of a variety of diseases, including arthritis, inflammatory bowel diseases, Alzheimer’s, Parkinson’s and diabetes.

New international research with a strong Danish contribution shows that statins may be part of the solution. In any case, the new study shows that obese people who took statins had, on average, a healthier gut microbiome than those who did not take statins.

“We must first state that statins do not cause people to lose weight, but they can help reduce the risk of developing some of the comorbidities that can be associated with obesity, such as atherosclerosis in both the brain and heart. And then our new results suggest that statins can improve the gut bacterial ecosystem among some obese people,” explains a leading researcher behind the study, Oluf Borbye Pedersen, Professor and Principal Investigator at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

The research results have been published in Nature.

200 million people take statins daily

Researchers estimate that about 200 million people worldwide take statins daily to lower their blood cholesterol levels, especially the “dangerous” LDL cholesterol.

High levels of LDL in the blood are associated with various atherosclerotic diseases and the development of blood clots.

“Statins are a success story, and one thing we wanted to find out in our research was how statins affect the gut microbiome,” says Oluf Borbye Pedersen.

Unhealthy gut microbiome is associated with many diseases

The researchers in the EU-funded MetaCardis consortium examined the composition and function of gut bacteria among 900 people from Denmark, Germany and France.

Instead of identifying all the hundreds of species of bacteria individually and examining the relationships between them, the researchers classified them into four enterotypes based on the bacterial ecosystem in the gut.

Previous research has shown that the enterotype called Bacteroides2 (Bact2) is known to be present in the intestines of some people with many chronic diseases and especially the inflammatory bowel diseases ulcerative colitis and Crohn’s disease.

Bact2 is low in health-promoting bacteria.

“We have also previously seen that Bact2 is abundant in the intestines of some obese people,” explains Oluf Borbye Pedersen.

Some obese people have too many unhealthy gut bacteria

The researchers analysed the gut microbiome of the participants in the trans-European study using sequencing of gut bacterial DNA. Among lean or overweight participants with a body mass index (BMI) less than 30, 4% had the harmful Bact2 enterotype in their gut.

The researchers examined the bacterial gut microbiome of obese participants with a BMI over 30 and found that 18% had the Bact2 enterotype.

However, only 6% of the obese participants who took statins to lower their cholesterol levels had the Bact2 enterotype.

A large study with 2,345 people in Belgium subsequently confirmed the result.

“This indicates that statins may help to bring the composition and function of the gut bacteria of some obese people into better balance, since they have many unhealthy gut bacteria and lack several beneficial bacteria. This is one of the first times that we have seen that a frequently used drug can positively affect the gut microbiome,” says Oluf Borbye Pedersen.

Statins also reduce inflammation

Oluf Borbye Pedersen tells that statins are also known to have other positive effects on health. They lower the level of C-reactive protein in the blood, a marker of inflammation.

Inflammation results from an overactive immune system, and moderate inflammation is present in many chronic conditions, including obesity, cardiovascular diseases, arthritis and psoriasis.

C-reactive protein in the blood is elevated among people with a relatively high abundance of Bact2 in their gut, but C-reactive protein levels decrease among obese people who take statins. Oluf Borbye Pedersen says that a healthier microbial community may be one reason.

“When people take statins, the quantity of Bact2 in the gut falls, causing inflammation to decline as well. Some of the bacteria in the Bact2 enterotype have the potential for triggering inflammation. Whether they do so in real life still remains to be tested in proper and comprehensive controlled clinical trials over a long time frame. But experiments with rats suggest that statins affect the microbial community,” says Oluf Borbye Pedersen.

Other drugs disturb the healthy composition of gut bacteria

Oluf Borbye Pedersen says that the research result is very encouraging because several other drugs negatively affect the gut microbiome.

For example, this applies to the antacids called proton-pump inhibitors that millions of people take every day. A few years ago, such antacids went from being prescription drugs to being available over the counter, and many people therefore take antacids regularly if they have acid reflux, gastritis or the like.

The problem with antacids is that they reduce the acidity of the gastric juices, and this means that bacteria from the oral cavity can survive through the gastric juices and establish themselves in the intestines, where they do not belong.

“People who take antacids have an altered gut bacteria profile, and one negative effect seems to be an increased risk of developing some types of colon cancer,” explains Oluf Borbye Pedersen.

Oluf Borbye Pedersen is excited about upcoming placebo-controlled clinical trials to clarify whether statins reduce atherosclerosis by not only lowering cholesterol but also by helping to promote enterotypes of health-promoting gut bacteria that reduce inflammation in the blood vessels and throughout the body.

“That is the real question to address, but we have to wait a few years to get the answer,” he adds.

Statin therapy is associated with lower prevalence of gut microbiota dysbiosis” has been published in Nature. Several authors are employed at the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

Oluf Borbye Pedersen
Professor
Oluf Pedersen and his research team contribute to gain novel insights into the complex and multifactorial aetiology of type 2 diabetes, obesity and cardiovascular disorders – scientific efforts that aim for novel approaches to prevent and treat these common disorders which are in epidemic growth. Applying a variety of biological samples, technologies and statistical-genetics methods the researchers are focused on discovering genomic variation that predisposes for common cardio-metabolic disorders. The genomic discoveries are further characterized in genetic-physiology studies of disease intermediary traits and in large-scale studies of genetic-epidemiology elucidating the interaction of gene variants with health behavior (unhealthy dietary habits, sedentary lifestyle and other environmental factors). Another major research effort is centered at studies of the role of the gut microbiota in primarily metabolic health and risk of metabolic disorders. Here the research team is doing quantitative metagenomics to characterize the human gut microbiome at levels of microbial genes, various taxa and derived functional potentials. Suspected human pathogenic microbiota is studied mechanistically in animal models.