Scientists have learned about the effect of intestinal inflammation on heart function
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- Scientists have learned about the effect of intestinal inflammation on heart function
Chronic intestinal inflammation can disrupt the functioning of the heart through changes in the microbiota and immune cells. Researchers from the University of Georgia in the USA have shown this mechanism in experiments on mice.: bacterial signals altered the behavior of immune system cells and contributed to the pathological enlargement of the heart muscle. How the intestine can affect another organ and what these results mean for people with inflammatory diseases — in the Izvestia article.
Why does intestinal disease affect the entire body?
Abdominal pain and digestive disorders are the most obvious manifestations of inflammatory bowel diseases. However, the effects may extend beyond the digestive system. For example, in Crohn's disease, inflammation sometimes affects the joints, skin, and eyes. Therefore, the condition of the intestine cannot be considered in isolation from the health of other organs.
It is important to distinguish these diagnoses from irritable bowel syndrome. It can also be accompanied by pain and changes in stool, but by itself it does not cause tissue damage characteristic of inflammatory diseases. The new work is devoted to chronic colitis, so it is impossible to transfer its conclusions to any bloating or discomfort in the abdomen.
The association of inflammatory bowel diseases with heart complications has already been noted in human studies. In the work of the Karolinska Institute, published in 2024, scientists compared more than 80 thousand patients with such diagnoses and about 400 thousand people from the general population. The patients had a 19% higher relative risk of heart failure.
This does not mean that 19% of patients developed heart failure. According to the authors, the difference corresponded to one additional case for every 130 patients over 20 years. The study revealed a statistical link, but did not establish its cause. A possible biological mechanism was studied by a team from Georgia.
What showed the transfer of intestinal bacteria
The scientists used a mouse model of chronic colitis, a long—term inflammation of the colon. They studied the composition of the intestinal microbiota, the metabolism in immune cells, and the state of the heart. Heart function was assessed using ultrasound, and tissue changes were assessed under a microscope.
Cardiac function disorders, hypertrophy and fibrosis were found in animals with colitis. Hypertrophy means an increase in heart muscle cells, while fibrosis means an accumulation of connective tissue. These changes were accompanied by metabolic restructuring and mitochondrial dysfunction in circulating immune cells.
To test the role of microorganisms, the researchers transferred the intestinal microbiota from mice with colitis to a healthy animal. This turned out to be enough to alter the metabolism in the immune cells of the recipients and cause disorders in the heart.
This experience helps to understand the direction of communication. If the altered microbiota only accompanies the disease, its transfer does not necessarily have to reproduce the consequences in another organism. Here he also contributed to the appearance of cardiac disorders. This is an argument in favor of the causal role of the microbiota in the experimental conditions.
"Our study suggests that chronic intestinal inflammation can affect the heart through changes in the gut microbiota and immune cells," said Jun Zou, a researcher at Georgia State University's Institute of Biomedical Sciences.
How does the bacterial signal reach the heart
Microbiota is a community of microorganisms that inhabit the intestine. In chronic colitis, its composition changes. Such a disorder is called dysbiosis: it is about changing the ratio of microorganisms, and not about one specific bacterium, which explains all the consequences of the disease.
Lipopolysaccharide, or LPS, turned out to be one of the important participants in the discovered mechanism. It is a component of the outer shell of some bacteria. If the intestinal barrier is disrupted, it can enter the bloodstream and affect immune cells. Thus, it is not necessary for the bacteria themselves to enter the heart muscle in order to affect the heart. Their molecules and the body's reaction to them can become a connecting link.
In the study, LPS acted through the TLR4 receptor— a molecular "sensor" of the immune system. Next, the protein, which the authors designate as GBP1, was activated. The title of the work also indicates mouse GBP2b: this is the corresponding protein studied in animal experiments.
Under the influence of the bacterial signal, the work of immune cells changed. They moved more actively into the heart, where they could contribute to the pathological enlargement of the heart muscle and deterioration of its function. Zou explained that signals from the gut can change immune cells so that they begin to migrate to the heart and participate in the development of these disorders.
Why cellular "power plants" are important
To understand the next step, you need to pay attention to the mitochondria, the structures inside the cell that provide most of the energy it needs. They are often compared to power plants. If the work of mitochondria changes, it can affect the behavior of the cell itself.
The authors found that after exposure to LPS, the GBP1 protein moved to the mitochondria and interacted with proteins regulating their separation. This contributed to mitochondrial fragmentation and oxidative stress, a condition in which an excess of reactive oxygen species can damage cellular structures. Among the important participants in heart damage, the researchers identified macrophages, cells of the immune system.
As a result, intestinal inflammation triggered a sequence of changes far beyond the original focus: the microbiota changed, bacterial signals entered the blood, the immune cells were rebuilt, and then they moved to the heart.
A pathological enlargement of the heart muscle does not mean that the heart is getting stronger. In diseases, thickening, enlargement, or increased stiffness of the heart muscle may prevent it from pumping blood efficiently. As explained by the National Heart, Lung, and Blood Institute of the USA, such changes can be accompanied by a weakening of cardiac function.
The second way is microscopic transmissions between cells.
Researchers have discovered another way of transmitting the signal. During colitis, GBP1 levels increased in exosomes, small membrane vesicles that cells secrete into the external environment.
Exosomes can be compared to parcels: they carry biological molecules and help cells exchange signals. Such bubbles are able to circulate in the body, and the recipient cells are able to capture their contents.
One of the senior authors of the work, Ye Ding, a researcher at the Institute of Biomedical Sciences at the University of Georgia, also pointed out the possible significance of the results for studying heart damage during infections. Many pathogens strongly activate proteins of the GBP family.
At the same time, GBP1 itself performs important protective functions. As Dean emphasized, during infection, it participates in antimicrobial protection, but excessive or impaired activation may inadvertently contribute to the deterioration of the heart.
The control of inflammatory disease and attention to the condition of the heart are already important for patients. Treatment of ulcerative colitis helps to suppress inflammation and maintain remission, and the authors of the Karolinska Institute study emphasize the need to take into account the cardiovascular health of people with inflammatory bowel diseases. The new work does not change the doctor's prescription, but provides an additional explanation for why monitoring such patients should not be limited to the digestive system.
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