Cooperation between gut and brain - modulating psyche, muscles and immune system
In recent years, our microbial co-inhabitants in the intestine have had an almost sensational career thanks to intensive research. Until a few decades ago, they were little known and were regarded at best as auxiliaries in digestion and as suppliers of a few vitamins. This has changed thoroughly. Every year, microbiome research brings to light findings to an astonished public that hardly anyone would have previously associated with the intestinal flora known as the microbiome. Not everything has been researched down to the last detail. We only know a lot from animal experiments, the results of which can only be transferred to humans with caution. Nevertheless, we already have a fairly comprehensive overview of what the intestinal flora does and could do.
Intestinal flora is diverse and unique like a fingerprint
Every human being has a typically composed intestinal flora that is supposed to be as unique as a fingerprint. This is one of the basic findings of the Human Microbiome Project, which set itself the goal of analysing the complex ecosystem called the human microbiome of as many people as possible. The researchers paid particular attention to the intestinal flora, as it is probably the most important part of the microbiome. It is mainly home to bacteria, but also viruses and fungi. So far, about 1000 different species of bacteria have been identified. Since the identification methods are constantly being refined, it is to be expected that the number of newly discovered bacterial co-inhabitants will increase even further. Despite great variability, however, researchers have also identified patterns in the composition of gut flora that can be grouped into three types of gut flora known as enterotypes. Scientists are currently working on correlating these individual enterotypes with certain human characteristics.
The gut talks to the brain - What the gut-brain axis does
The term "gut-brain axis" describes a communication pathway between the gut and the brain that had gone unnoticed for a long time and was also not thought to be possible. It is nothing less than the control of brain functions by the intestine. For many, this is still difficult to digest today, as it gives the term "gut feeling" a completely new meaning. So what is behind the gut-brain axis and how should we imagine brain functions to be controlled by the gut? Of course, the conversation between the gut and the brain must not be imagined in the literal sense. Even if the nature of the communication has not yet been clarified in all parts or has passed the stage of animal experimental observations, research today believes to know that the intestine with its intestinal flora can contact the brain for the exchange of information in at least three ways. These include in particular the vagus nerve, which connects the intestine and brain in a communicative way. But hormones and neurotransmitters such as serotonin, dopamine or melatonin also play an important role. They are all produced in the intestine to act in nerve cells of the brain. Furthermore, metabolic products of the intestinal bacteria are involved in communication. Butyric acid, for example, can change the properties of the blood-brain barrier. Immune molecules and cytokines produced by gut bacteria can also influence the physiology of nerve cells.
Gut microbiome influences psyche - There could be psychobiotics
Studies on the composition and function of the gut flora indicate that the nature of its composition influences brain function and mental balance. If the intestinal flora is disturbed and bacteria with a damaging influence gain the upper hand, this correlates with mental well-being disorders up to psychiatric diseases such as depression, as a group of researchers from Belgium could prove. The researchers examined a good 1000 stool samples for their microbial composition and correlated this with the mental health of their owners. In the process, they identified bacterial strains that occur more frequently in people with good mental health. Conversely, the absence of these bacteria indicated mental disorders including depression. It becomes exciting when it comes to remedying mental disorders through the targeted administration of such bacteria. There is not yet sufficient data on this that would allow a cocktail of psychoactive bacteria to be used therapeutically as psychobiotics. It would be desirable in any case, since the psychotropic drugs available today have their downsides.
Intestinal flora controls muscle growth - intestinal bacteria act like anabolic steroids
Targeted training activities promote muscle growth and can compensate for pathological or age-related muscle loss. Whether the microbiome in the gut also plays a decisive role in this process is not yet fully understood. Animal studies on mice indicate that the microbiome in its entirety supports the muscle building training of the animals. For this purpose, mice first had their microbial flora completely destroyed by antibiotics. Afterwards, the animals trained on the running wheel just like their untreated conspecifics. In animals with an intact microbiome, the training effect, measured as muscle mass formed, was significantly greater than in animals without a microbiome. Whether specific bacterial strains or the anabolic substances they produce are responsible for the anabolic effect will be clarified in further studies.
Microbiome modulates immunity - Non-specific immune defence is activated
How can the immune system react quickly to pathogens and protect humans from infections? One answer is provided by the microbiome. Roughly divided, the immune system consists of two divisions, the innate, non-specific immune system and the adaptive, specific immune system. The microbiome communicates with structures of the innate immune system called dendritic cells and puts them in a permanent state of readiness to react. Activated in this way, the innate immune system is quickly able to react to intruders from the respiratory tract, the intestine or via the skin and, in a second step, to alert the specific immune system. If the activation fails to occur due to disturbances of the microbiome, the immune defence cannot repel the attacker as quickly, as experiments with germ-free mice have shown. This also delays the alerting of the specific immune system. Which biomolecules are responsible for the communication between the microbiome and the immune system is being researched by immunologists at the Berlin Charité.
Colonisation resistance - intestinal bacteria protect against pathogens
A healthy intestinal flora as part of the human microbiome is composed of a large number of microorganisms. Modern analytical methods are constantly uncovering new, previously unknown species of bacteria. At present, research assumes at least 1000 different intestinal bacteria and a largely unknown number of viruses and fungi. This microbial multitude is an important component of colonisation resistance, which suppresses the emergence of other bacteria and protects against pathogens. In this way, a healthy intestinal flora ensures that no pathogens can multiply in the intestine and enter the bloodstream via the intestinal mucosa.
Microbiome is a bioreactor - bacteria produce important biomolecules
Communication between the gut and the brain takes place both nervally via the vagus nerve and humorally via neurotransmitters and neurohormones. Most of the humoral messengers are produced in the intestine by intestinal bacteria, but also in the brain. This ensures mutual communication. Serotonin, noradrenalin and dopamine are involved in humoral communication. Serotonin is also known as the happiness hormone and contributes significantly to mental well-being.
Less well known are short-chain fatty acids, which are also produced by intestinal bacteria. They include butyric acid (butanoate) and valeric acid (pentanoate), which, according to a study by the universities of Würzburg and Marburg, make immune cells more aggressive. If it were possible to use this effect of the two fatty acids in a targeted therapeutic way, cancer therapies could be made more effective. This is the hope of the researchers.
Bacteria of the intestinal flora also produce vitamins. These include biotin, folic acid, vitamins B2 and B12 as well as vitamin K. It is known that a considerable part of the daily requirement of vitamin B12 is produced by intestinal bacteria.
Conclusion: Anyone who believes that everything is known about the intestine and its intestinal flora and that nothing new can be discovered is mistaken. Current research programmes are looking very intensively for possibilities to treat some diseases through targeted changes in the intestinal flora. This goes as far as the complete replacement of a pathologically altered intestinal flora by a healthy one with desired characteristics.
Source: Valles-Colomer, M., et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol 4, 623-632 (2019). https://doi.org/10.1038/s41564-018-0337-x
Taylor R. Valentino, et al. Dysbiosis of the gut microbiome impairs mouse skeletal muscle adaptation to exercise, The Journal of Physiology, First published: 26 September 2021,https://doi.org/10.1113/JP281788
Laura Schaupp et al. Microbiota-Induced Type I Interferons Instruct a Poised Basal State of Dendritic Cells, Cell Volume 181, ISSUE 5, P1080-1096.e19, May 28, 2020DOI:https://doi.org/10.1016/j.cell.2020.04.022
Maik Luu, et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nature Communications, https://doi.org/10.1038/s41467-021-24331-1