Changes in the gut may contribute to brain disease, says neurologist and scientist Lenka Krajčovičová
Neurologist Lenka Krajčovičová, in addition to diagnosing and treating patients with neurodegenerative diseases at the Center for Cognitive Disorders at the First Department of Neurology of St. Anne’s University Hospital in Brno, is also involved in research on Alzheimer’s and Parkinson’s disease at ICRC and NEUR-IN. She has now embarked on studying the gut microbiome and its impact on the development of these diseases. How are our gut and brain connected, and how does the health of one organ affect the condition of the other?
What Does the Term Gut Microbiome Encompass?
It refers to the collection of microorganisms that inhabit the intestinal lining. This includes all microorganisms—not just bacteria but also viruses, yeasts, and other types of microbes. The term microbiome also encompasses their environment, such as the substances these organisms produce and essentially the entire ecosystem associated with them.
When Did the Discussion About the Gut’s Influence on the Brain Begin? When Did It Become a Subject of Scientific Study?
This connection has been known for quite some time, but research into the microbiome in relation to neurodegenerative diseases has gained momentum only in the last ten years.
Why Did the Study of the Gut Microbiome Catch Your Attention as a Neurologist?
Originally, I became interested in this topic in relation to Parkinson’s disease. It has been known for some time that this disease is somehow linked to the digestive system. Before Parkinson’s patients develop their first symptoms and come to our clinic, they often experience gastrointestinal issues—typically constipation—which then continues throughout the course of the disease. This led researchers to investigate the relationship between the gut and the disease.
Detailed gut analyses revealed pathological changes—first, the same protein responsible for neurodegeneration in the brain, synuclein, was found in the intestines of patients. Additionally, the gut may experience a decrease in neurotransmitters, which are substances that mediate nerve signaling. This led to the hypothesis that the microbial composition of the gut might play a role. It is well known that microbiome imbalances are linked to other diseases, so it is reasonable to hypothesize that these changes might contribute to the development of neurodegenerative diseases.
Does This Mean That the Gut Is Not Just an Indicator of Disease—A Place Where Early Symptoms Can Be Observed Before They Appear in the Brain—But a Cause of the Disease Itself?
The communication is bidirectional. Yes, changes in the gut can affect brain function and contribute to the development of these diseases, but the brain can also influence the gut. This connection is known as the gut-brain axis. It happens either through direct nerve communication—the brain can regulate gut motility via the vagus nerve—or through neural endings in the gut that send signaling molecules to the brain.
There is also an indirect pathway: various substances, primarily nutrients, enter the bloodstream from the gut. Many cells in the gut, whether they belong to the organ itself or to the microorganisms living in it, release signaling molecules that serve to inform the brain. A common example is the signaling that occurs after eating, letting the brain know that the body is full and no longer needs to consume more food.
Gut microbiome helps control intestinal digestion and the immune system
Besides Influencing the Development of Alzheimer’s and Parkinson’s, It Is Also Said That the Gut Affects Our Mood, Emotions, Experiences, Stress Responses, and Cognitive Functions. How Are These Connected?
The mechanism of this connection is similar. And again, it works in both directions. When a person is stressed, the brain, which processes stress stimuli, can send signals to the gut, leading to the suppression of basic needs, such as appetite, and slowing down digestive processes.
On the other hand, when a person consumes food beneficial for the microbiome, the gut flora produces serotonin, which contributes to good mood, well-being, and a sense of happiness. Conversely, an improper diet can disrupt the microbial balance in the gut, leading to the overproduction of substances that negatively affect the intestinal lining and can have distant effects on other parts of the body, including the brain.
How Can We Positively Influence Our Gut Microbiome?
A healthy lifestyle is key. The most important factor is a sufficient intake of fiber, which serves as the primary food source for the microbiome. Highly processed foods and ready-made meals, which are low in nutrients but high in fat and sugar, harm the microbiome. Regular physical activity also supports gut health—when the gut is well-supplied with blood, it functions much better. When comparing the microbiomes of people with a healthy and unhealthy lifestyle, their compositions are entirely different.
The Gut Microbiome Is One of the Most Important Components of Our Immune System and Can Influence Inflammatory Processes in the Body. Inflammation in the Brain Is Linked to the Development of Alzheimer’s Disease. Could These Be Related?
Yes, this is still a hypothesis, but we assume there is a connection. An unhealthy or disrupted microbiome triggers an immune response—a low-grade, chronic inflammation that doesn’t have obvious symptoms. A person wouldn’t notice it, as it doesn’t present like a typical infection with fever or other clear signs.
However, the immune system becomes activated, and molecules produced by an inflammatory microbiome can travel to the brain. Whether this leads to disease depends on other factors, including genetic predisposition. Chronic inflammation, however, can contribute to the formation and accumulation of harmful proteins in the brain, which drives the process of neurodegeneration.
When Can We Diagnose Inflammatory Processes in the Brain?
We can detect the presence of beta-amyloid protein clusters in Alzheimer’s disease relatively early. There are specific diagnostic methods for this, including lumbar puncture to analyze cerebrospinal fluid or positron emission tomography (PET). PET imaging uses a specially labeled radionuclide that, once injected into the patient’s bloodstream, accumulates in amyloid plaques in the brain. Radiologists can then detect these plaques using a specialized camera.
This examination is minimally invasive and much more tolerable for the patient compared to a lumbar puncture. Amyloid plaques can appear in the brain 20 to 30 years before symptoms develop. However, we do not know which individuals in the population will actually develop the disease, so this method cannot be used as a general screening tool—it is simply too expensive. However, if someone begins to show symptoms and is in the age group where the risk increases (around 50–60 years old), one of these tests should be performed.
If We Start Noticing Memory Decline at a Young Age—In Our 30s or 40s—Such as Forgetting Names or Struggling to Recall Certain Terms, Should We Be Concerned?
It is highly unlikely that Alzheimer’s disease would develop in someone in their 30s. Alzheimer’s is strongly associated with aging and older age. The exception would be cases of hereditary Alzheimer’s, which can develop as early as the 40s. However, individuals at risk of the hereditary form would typically be aware of their family history. In such cases, we refer the patient for genetic testing immediately, but this form of the disease is extremely rare.
Does Genetics Play the Main Role in the Development of Alzheimer’s Disease?
In most cases, it is a combination of multiple factors, but genetics is one of the most significant. However, it usually involves predisposition—an increased susceptibility to the disease—rather than a direct cause. Some of the genes associated with Alzheimer’s are already known, with APOE4 being the most well-known. Individuals with two copies of this gene have a significantly higher risk of developing the disease and are more likely to experience it at a younger age.
That being said, Alzheimer’s in a person in their 30s or 40s is exceptionally rare. The situation is different for Parkinson’s disease, which can affect much younger patients.
If Someone Knows That Alzheimer’s Disease Has Appeared Multiple Times in Their Family, Can They Find Out If They Carry the APOE4 Gene?
Genotyping for APOE is a relatively common and accessible test. It is fairly inexpensive, and in some cases, insurance may cover it. However, individuals can also choose to have it done privately. When it comes to genetic panels, the situation is more complex. These panels include multiple genes, not just APOE, and their composition can vary—so a consultation with a geneticist is necessary.
A positive result does not necessarily mean that a person will develop the disease. Genetic predisposition means an increased risk, but we cannot predict when—or even if—a patient will actually develop Alzheimer’s.
The prevalence of Alzheimer’s disease in society is constantly increasing.
What Can We Do to Delay the Onset of Alzheimer’s?
Besides maintaining a healthy lifestyle, cognitive training is key. It’s important to keep the brain active. Even in retirement, people should avoid thinking that they’ve “done enough in life.” (laughs) Staying engaged for as long as possible is crucial. A great way to do this is by learning a new language, reading frequently, or taking up hobbies they previously didn’t have time for. Maintaining a social life is also important, as social isolation is a well-known risk factor for dementia.
Has Your Research on Gut Microbiota and Its Influence on Neurodegenerative Diseases, Conducted at ICRC and NEUR-IN, Yielded Any Concrete Results? Have You Discovered Anything Significant?
We have already analyzed half of the patient samples and will soon have a complete cohort of volunteers. The next step will be a follow-up evaluation after a year to observe whether and how the microbiome changes over time as the disease progresses.
We have compared Alzheimer’s and Parkinson’s patients with healthy individuals, and there are clear differences. We are also comparing patients in the early stages of Alzheimer’s and Parkinson’s—who have only mild symptoms—with those in more advanced stages. So far, we have observed lower microbiome diversity in patients with Alzheimer’s and Parkinson’s, meaning fewer microbial species are present.
We are analyzing not only gut microbiota but also nasal and oral microbiota. Interestingly, the most significant differences so far appear in the nasal microbiome, particularly in Parkinson’s patients. However, we are still in the early stages of our research. We are also looking for correlations between microbiome composition and other factors—participants fill out questionnaires on lifestyle, sleep quality, chronic illnesses, and more.
Additionally, in Dr. Jan Frič’s laboratory, we will be analyzing immune phenotypes to investigate links between microbiome changes and immune system alterations. Our initial findings suggest there is indeed a connection…
Do You Think This Research Could Lead to New Treatment Methods, Such as Diagnosing Gut Microbiota and Then Adjusting Diet and Lifestyle Individually?
Personally, I believe it could. Most importantly, I think this research should clarify the relationship between the microbiome and disease—specifically, the mechanisms that contribute to disease development. By identifying an individual’s microbiome, we could then implement targeted measures aimed at improving health and mitigating negative effects.
It might even be possible to develop personalized probiotics. While probiotics are already available as dietary supplements in any pharmacy and can be beneficial, for example, after taking antibiotics, they do not create long-term changes in the microbiome. The mechanisms needed to induce a more lasting shift in gut microbiota still require further research.
