AI Decodes the Hidden Communication of Intestinal Microbes

Gut bacteria play an important role in human health, influencing everything from digestion to the immune system to mood. However, the complexity of the microbiome is staggering. The sheer number of bacterial species and their interactions with human chemistry have made it difficult for scientists to fully understand their effects. In a groundbreaking move, researchers at the University of Tokyo applied a type of artificial intelligence known as a Bayesian neural network to study gut bacteria. Their aim was to uncover relationships that are often overlooked by conventional data analysis methods.

Neural Network Examines Huge Data Set on Gut Microbes to Provide Clues to Health

While the human body contains around 30 to 40 trillion human cells, the gut alone is home to around 100 trillion bacterial cells. In other words: We carry more bacterial cells than our own cells. Intestinal microbes are microorganisms such as bacteria, fungi, viruses and archaea that live in the human digestive tract and together form the so-called intestinal microbiome. Most of them are found in the large intestine. Despite their tiny size, they play a crucial role in our health. They support digestion by breaking down food components that our own body cannot utilize, especially dietary fibres. This produces important metabolic products such as short-chain fatty acids, which strengthen the intestinal wall and provide the body with energy. Many intestinal bacteria also produce vital substances, for example vitamin K or certain B vitamins. The microbes also produce and modify thousands of compounds known as metabolites.

These small molecules act as chemical messengers, circulate through the body and influence metabolism, the immune system and even brain function. In addition to their role in digestion, gut microbes also protect against pathogens by eliminating harmful germs and strengthening the intestinal barrier. A large part of the immune system is located in the gut, and the microbes help to train it and keep it in balance. In doing so, they help to regulate inflammation and prevent adverse reactions such as allergies. In addition, gut microbes are in close contact with the nervous system. Via the so-called gut-brain axis, they influence our mood, our stress behavior and possibly even cognitive processes. They are also important for our metabolism: they help determine how many calories we absorb from food, how our sugar metabolism works and how likely it is that we will become overweight. Understanding how certain bacteria produce certain metabolites could open up new ways to promote general health.

“The problem is that we are just beginning to understand which bacteria produce which human metabolites and how these relationships change in different diseases,” explained project researcher Tung Dang from the Tsunoda lab in the Department of Biological Sciences. “By accurately mapping these relationships between bacteria and chemicals, we could potentially develop personalized treatments. Imagine being able to grow a specific bacterium to produce beneficial human metabolites, or develop targeted therapies that modify these metabolites to treat diseases.” The biggest challenge lies in the sheer volume of data. With countless bacteria and metabolites interacting with each other in complex ways, it is extremely difficult to identify meaningful patterns. To tackle this problem, Dang and his team turned to advanced artificial intelligence (AI) methods.

Their system, called VBayesMM, uses a Bayesian approach to recognize which groups of bacteria significantly affect certain metabolites. It also measures the uncertainty of its predictions, helping to avoid exaggerated but incorrect conclusions. “When tested with real data from studies on sleep disorders, obesity and cancer, our approach consistently outperformed existing methods and identified specific bacterial families that match known biological processes,” says Dang. “This gives us confidence that it is detecting real biological relationships and not just meaningless statistical patterns.”

Understanding the Strengths and Limitations of the System

Because VBayesMM can recognize and communicate uncertainty, it provides researchers with more reliable insights than previous tools. Although it is optimized for big data, the analysis of large microbiome datasets remains computationally challenging. Over time, however, these costs should decrease as computing power improves. The system also works best when large bacterial data is available compared to metabolite data; otherwise, accuracy may decrease. Another limitation is that VBayesMM treats bacteria as independent actors, even though they often interact in complex, interdependent networks.

The researchers plan to work with more comprehensive chemical datasets that capture the full range of bacterial products, although this poses new challenges in determining whether chemicals originate from bacteria, the human body or external sources such as food. The experts also want to make VBayesMM more robust when it comes to analyzing different patient populations by incorporating bacterial ‘pedigree’ relationships to make better predictions and further reduce the computational time required for analysis. For clinical applications, the ultimate goal is to identify specific bacterial targets for treatments or nutritional interventions that could actually help patients, moving from basic research to practical medical applications. By using AI to explore the vast and complex world of gut microbes, researchers are getting ever closer to unlocking the potential of the microbiome to transform personalized medicine.

Gut Microbes Could Also be the Key to New Ways of Preventing and Treating Heart Disease

Cardiovascular disease claims nearly 20 million lives every year, making it the leading cause of death worldwide. While genetic factors and lifestyle clearly influence a person’s heart health, scientists are now discovering that microorganisms that live in the gut may also have an important influence. These microbes appear to be significantly involved in the development of coronary heart disease (CHD), although their exact role has long been unclear.

Recent research suggests that the gut microbiome can promote CHD through various biological pathways and influence inflammation and metabolic processes in a way that affects the arteries. However, the specific bacteria responsible for this – and how they contribute to disease progression – remains unclear.

Mapping Microbes in Coronary Heart Disease

Researchers in Seoul are beginning to unravel this mystery. In an article in mSystems, a team led by Dr. Han-Na Kim of the Samsung Advanced Institute for Health Sciences and Technology at Sungkyunkwan University investigated how gut microbes interact with the cardiovascular system. “We went beyond identifying ‘what bacteria live there’ and found out what they actually do in the heart-gut connection,” Kim explained.

Coronary artery disease (CAD) is a disease of the coronary arteries, the blood vessels that supply the heart muscle with oxygen and nutrients. In this disease, the vessels constrict due to deposits of fat, cholesterol and calcium, known as plaques. This gradual process is called arteriosclerosis or vascular calcification. The narrowing means that less blood reaches the heart muscle, especially when the heart has to work harder, for example during physical exertion or stress. This often causes a feeling of pressure, tightness or pain in the chest, known as angina pectoris. If a coronary artery is completely blocked, part of the heart muscle no longer receives oxygen, which leads to a heart attack.

CHD does not occur suddenly, but develops over many years. The most important risk factors include smoking, high blood pressure, diabetes, elevated LDL cholesterol levels, lack of exercise, an unhealthy diet, obesity, genetic predisposition and chronic stress. In addition to chest pain, typical symptoms include shortness of breath, rapid fatigue on exertion and pain that can radiate to the arm, shoulder, jaw or back. Coronary heart disease is dangerous because it often goes unnoticed for a long time and significantly increases the risk of heart attack, heart failure and sudden cardiac death.

The team analyzed stool samples from 14 people with CHD and compared them with samples from 28 healthy participants using metagenome sequencing, a powerful technique that can identify all the DNA in a sample. This approach allowed them to reconstruct the genetic composition of individual microbes. From this analysis, the researchers identified 15 bacterial species associated with CHD and mapped the pathways linking these microbes to disease severity.

Inflammation, Imbalance and Microbial Shifts

According to Kim, “Our high-resolution metagenomic map shows a dramatic functional shift toward inflammation and metabolic imbalances, a loss of protective short-chain fatty acid producers such as Faecalibacterium prausnitzii, and over-activation of metabolic pathways such as the urea cycle that are linked to disease severity.” The findings suggest that the gut ecosystem in people with CAD undergoes significant changes that promote inflammation and disrupt normal metabolic processes. These changes could explain why the gut microbiome plays such an important role in cardiovascular disease.

Surprisingly, the study also showed that bacteria that are normally considered beneficial can sometimes become harmful. Microbes such as Akkermansia muciniphila and F. prausnitzii, which are often considered “friendly” species, appear to act differently depending on whether they come from a healthy or a diseased gut. This dual nature, Kim says, illustrates how context can turn even protective microbes into disease-causing agents.

The results also showed how complex it is to link specific bacteria to disease progression. Previous research had reported that certain species within the Lachnospiraceae family decline in people with CHD. However, Kim’s team found that other Lachnospiraceae species were actually increasing in abundance. “Lachnospiraceae may be kind of like the Dr. Jekyll and Mr. Hyde of the gut,” Kim said. Some species appear to be beneficial, while others can exacerbate disease. The big unanswered question now is which strains are beneficial and which cause problems.

On the Road to Precision Microbial Medicine

The researchers plan to combine microbial data with genetic and metabolic information to better understand how gut microbes affect heart disease at a mechanistic level. Their long-term goal is to develop precision-based treatments that use microbial insights to prevent cardiovascular disease before it develops.

Kim emphasized that prevention is the most promising approach to reduce the global impact of heart disease. Possible strategies could include microbial therapies – such as stool-based diagnostic screenings – or dietary interventions aimed at restoring beneficial bacteria or inhibiting harmful processes. By uncovering the specific bacterial species and biological mechanisms, scientists are one step closer to harnessing the gut microbiome as an effective tool for maintaining heart health.

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