What can we do today to improve our health by taking care of our microbiome? Could the microbiome in our mouth and gut help detect diseases in the future even before the first symptoms appear? Researchers at Rīga Stradiņš University (RSU) have already found answers to some questions, while continuing to investigate others.
What Is the Microbiome?
It is the collection of all microbes found in the human body. It can differ between organs, so it is possible to study, for example, the oral microbiome and the gut microbiome separately. Differences can even be observed within the same part of the body – the microbiome on the tongue differs from that found on the gums or the inner surface of the cheeks. The microbiome includes not only bacteria but also viruses and fungi. The microbiome has been studied worldwide for more than 20 years.
Microorganisms can both cause diseases and help the body perform important functions – they participate in the processing of nutrients, the functioning of the immune system and various metabolic processes.
Therefore, it is important for scientists to understand not only which microorganisms live in the human body, but also how their overall composition and activity change.
The Microbiome of Ancient Humans – More Diverse
When Alisa Kazarina, a leading researcher at the RSU Faculty of Dentistry, began studying the microorganisms of ancient humans during her doctoral studies, her main research material was dental calculus.
Kazarina explains: "I studied the microbiome of people who lived in the 16th and 17th centuries by analysing archaeological human remains. During the research, I realised quite quickly that if I wanted to have any hope of finding traces of ancient microbes, the only material where I could realistically look for them was dental calculus. My archaeologist colleagues brought me dental calculus from ancient humans, and I studied which ancient human microbes had remained there and compared them with what can be found in dental calculus today."
The researcher used sequencing – a method that makes it possible to read the genetic material of microorganisms preserved in dental calculus. As in other studies, the RSU researcher's work also confirmed that the microbiome of modern humans is "dying out" – its biological diversity is decreasing.
The researcher wonders whether these changes could somehow be linked to so-called diseases of civilisation. Perhaps the decline in microbiome diversity has been influenced by changes in people's lifestyles – their diet, environment and exposure to microorganisms in the surrounding world. For example, nowadays people more often live in cities, have less contact with the natural environment and use various antibacterial products.
How the Microbiome Develops in Early Childhood
Although the microbiome changes throughout life, the way it develops during the first three years of life is of great importance. These issues have been analysed in scientific studies by Ilze Maldupa, a leading researcher and lecturer at the RSU Faculty of Dentistry.
The development of the microbiome is influenced by the earliest conditions of life – the mode of delivery, breastfeeding, first foods and early dietary habits. For example, children born through vaginal delivery have a healthier microbiome compared to babies born by caesarean section. However, regardless of the mode of delivery, if the baby is subsequently exclusively breastfed (fed only breast milk until six months of age), their microbiome becomes more diverse and healthier compared to the microbiome of formula-fed children. Breast milk contains both microorganisms and substances that promote the growth of certain gut bacteria.
Thus, breastfeeding helps establish the child's gut microbiome and supports the development of the immune system, as well as promoting endocrine, nervous system and cognitive development.
When introducing complementary foods to a child, a varied diet is important, gradually including vegetables, fruits, cereals and other age-appropriate foods. These foods create a more favourable environment for gut microorganisms than industrially processed foods containing sugar. Ilze Maldupa emphasises that even the composition of ready-made baby food should be carefully examined – it often contains sugar even when it is stated that no sugar has been added.
Childhood is an important stage in microbiome development, but its composition is not predetermined for life. The microbiome continues to change in adulthood, influenced by diet, medications, lifestyle and the surrounding environment.
Could Microbiome Research Help Detect and Treat Diseases Earlier?
Microbiome research opens up new opportunities for disease diagnosis and treatment. Scientists are investigating whether changes in the microbiome could indicate the development of a disease even before the first symptoms appear, allowing it to be detected in time and possibly prevented. At the same time, researchers are looking for ways to treat certain diseases by deliberately influencing the microbiome.
One such study is the doctoral research of RSU doctoral student and gastroenterologist Ilona Vilkoite on the relationship between the gut microbiome and colorectal adenomas, or precancerous growths in the colon.
Adenomas are growths, some of which can develop into malignant tumours over time. Therefore, their early detection and removal are an important part of colorectal cancer prevention.
In her doctoral research, Ilona Vilkoite compared the gut microbiome of people with colorectal adenomas and people without such growths. Her research findings indicate that patients with colorectal adenomas had a reduced relative abundance of several microbial metabolic pathways, including those associated with the biosynthesis of vitamin K₂ (menaquinone), the fermentation of certain amino acids and the production of the short-chain fatty acid propionate.
"Our study showed that differences can already be observed not only in the composition of the gut microbiome but also in its functional potential at the stage of precancerous changes in the colon. This suggests that changes in microbiome metabolism could be associated with early processes of colorectal neoplasia. However, further research is still needed to determine whether these changes are one of the factors contributing to the development of the disease or a consequence of changes that are already present," explains Vilkoite.
The researcher found that the two groups of study participants differed not only in the composition of microorganisms but also in their potential activity.
"In patients with colorectal adenomas, we identified a reduced relative abundance of six microbial metabolic pathways. This means that the microbiome differs not only in terms of its microbial composition but also in its potential metabolic functions. Particularly interesting are the changes in processes associated with the production of vitamin K₂ and propionate, as these substances may play a role in regulating intestinal mucosal homeostasis and inflammation. However, the concentrations of these substances were not directly measured in our study.
These findings are consistent with other international studies suggesting that gut microbiome dysfunction may be one of the early mechanisms involved in the development of colorectal cancer," notes Ilona Vilkoite.
It should be noted that microbiome analysis does not yet replace the currently used colorectal cancer screening methods. However, such studies open up opportunities to understand disease development at a much more detailed level.
Meanwhile, Alisa Kazarina, continuing her microbiome research during her postdoctoral studies, focused on periodontitis – a disease that affects the gums and the tissues supporting the teeth. Changes in the oral microbiome and the body's inflammatory response play a significant role in its development.
The researcher is currently conducting a clinical study on how to effectively control harmful pathogens in periodontitis in a gentler way while preserving the balance of the oral microbiome, which is important for health. In the third stage of the disease, patients are usually prescribed strong antibacterial agents, such as a mouthwash containing chlorhexidine. Its use can have several noticeable side effects: taste perception may change, and dark stains may appear on the teeth. Moreover, with prolonged use, not only harmful bacteria are destroyed, but also those that are essential for health. This can have negative consequences for overall health. For example, bacteria living in the oral cavity reduce nitrates obtained from the diet, producing nitric oxide – a very important signalling molecule that helps maintain cardiovascular health. If these bacteria are destroyed, the amount of nitric oxide in the body decreases, which can lead to an increase in blood pressure.
Kazarina is investigating whether the treatment could be replaced with a mouthwash containing essential oils from medicinal plants grown in Latvia.
"We tested coriander, caraway and chamomile, but it was coriander oil that made it to the clinical study involving patients. Coriander grown in Latvia and cultivated by the Institute for Environmental Solutions has a unique chemical composition that makes it possible to effectively control harmful pathogens while preserving the balance of the oral microbiome, which is important for health," emphasises the researcher.
She has also turned her attention to another question – whether changes in the oral microbiome could help detect periodontitis earlier. Periodontitis can progress for a long time without pronounced symptoms, so patients often seek medical attention only when more serious tissue damage has already occurred. Therefore, another direction of research is how to study the oral microbiome in order to use it as an early diagnostic tool. It is possible that certain changes in the microbiome exist which, if detected in time, could prompt a person to seek medical attention early to reduce the risk of developing certain diseases. Moreover, oral microbiome analyses could also serve as a tool for monitoring treatment effectiveness, making it possible to track changes in the microbiome during and after therapy.
Does the Gut Microbiome Also Affect Depression and Anxiety?
The relationship between mental health and the gut microbiome is also being increasingly studied. You may have heard of the gut-brain axis – this is how scientists refer to the communication between the gut and the brain. The brain influences intestinal function, while processes taking place in the gut can affect brain function and well-being. This communication involves the nervous and immune systems, hormones and substances produced by gut microorganisms.
Alise Stugle, a graduate of the RSU study programme "Medicine", who is currently a resident physician in psychotherapy, analysed scientific literature on the potential role of the gut microbiome in the development of depression and anxiety in her final research paper. Here are some of the research findings.
Stress hormones can alter intestinal motility and permeability, while changes in the gut microbiome may be associated with the body's stress response.
Studies suggest a possible link between the gut microbiome, inflammatory processes and symptoms of depression or anxiety. An imbalanced microbiome can reduce neurotransmitter production and increase inflammation and oxidative stress.
It has also been demonstrated that healthy dietary habits may be associated with a lower risk of anxiety and depression by influencing the composition and functional activity of the gut microbiome, as well as reducing inflammation.
Scientists have found that patients with depression often have lower levels of certain bacterial groups, such as Firmicutes, which are involved in the production of short-chain fatty acids (SCFAs). SCFA deficiency can weaken the intestinal barrier, increasing permeability and inflammation. SCFAs have anti-inflammatory effects that help maintain the integrity of the intestinal barrier and reduce symptoms of depression.
Scientists are also studying the interaction of microorganisms with substances involved in the transmission of nerve signals and hormones that influence appetite, mood and stress regulation.
Stugle acknowledges: "Currently, treatment options targeting the gut microbiome are relatively limited. An increasing number of studies on psychobiotics are appearing in the scientific literature. Psychobiotics are agents aimed at influencing mental health by modulating the gut microbiome. These agents include prebiotics, probiotics, diet and exercise. In the future, a possible treatment for patients with irritable bowel syndrome and anxiety or depression could be targeted therapy with probiotics, used either alongside medications or independently."
Scientists still need to determine which microorganisms are the most important, who could benefit from interventions targeting the microbiome, and whether the observed effects are sufficiently long-lasting to be used in treatment.
What Can We Do for Our Microbiome Today?
Enough has already been discovered about the relationship between the microbiome and everyday habits to provide practical recommendations for improving the microbiome.
Ilona Vilkoite emphasises that studies show that a varied diet rich in fibre and polyphenols, which also includes fermented foods (kefir, yoghurt and fermented vegetables) and olive oil, can have a beneficial effect on the composition and metabolism of the gut microbiome. For example, it is recommended to regularly include vegetables, whole grains, legumes, fruits, berries, nuts and seeds in the diet.
Such dietary habits are also associated with more favourable indicators of inflammation and metabolic health. However, the mechanisms behind these benefits are complex, and not all of them can be directly attributed to changes in the microbiome.
Ilze Maldupa reminds us not to forget legumes, as they have a beneficial effect on the microbiome. "I recommend avoiding products whose ingredient lists need to be read – if a product is packaged and you cannot tell what it contains without reading the label, it cannot be healthy for either us or our bacteria. The term 'ultra-processed food' has been introduced worldwide, referring to all these industrially manufactured products, and it can almost always be equated with an 'unhealthy diet'," emphasises Ilze Maldupa.
Particular Attention Should Be Paid to Added Sugar Consumption, Especially in Childhood
A literature review conducted by the RSU Institute of Public Health identified studies that used historical data on restrictions on sugar availability during and after the Second World War. These circumstances created a unique natural experiment that allowed researchers to assess the relationship between sugar intake in early life and health later in life.
The studies found that people whose sugar consumption was restricted from the time of their mother's pregnancy through the first years of life had a lower risk of certain metabolic and cardiovascular diseases later in life.
Sugar also affects the environment of oral microorganisms. Frequent consumption of sugary foods and drinks promotes the formation of acids in dental plaque, which in turn damage tooth enamel and contribute to the development of dental caries.
Antibacterial products should also be used thoughtfully. Alisa Kazarina reminds us that not all microorganisms are harmful. Therefore, strong antibacterial mouthwashes should not be used for prolonged periods without necessity and the recommendation of a specialist.
Science has already helped us understand how important the microbiome is to human health. Researchers around the world, including at RSU, continue to investigate how changes in the microbiome are linked to the development of diseases and whether this knowledge will make it possible to detect, prevent or treat diseases earlier in the future. Meanwhile, we can already take care of our microbiome today by adopting science-based healthy habits in our daily lives.
