
In recent years, there has been active research in science and medicine on the properties of the gut microbiota (intestinal microbiome) of humans and other related living organisms. To date, a connection has been established between the disruption of the microbiome composition and the development of functional gastrointestinal disorders, such as irritable bowel syndrome (6).
Changes in the composition of gut microbiota can also play a significant role in inflammatory bowel diseases due to the disruption of the local immune response in the intestine (7). The link between microbiome changes and increased risk of obesity, insulin resistance, and colorectal cancer has also been proven in studies (4,5). Based on the presented data, we can conclude that maintaining a healthy microbiome composition, in which the gut functions normally and there is no disruption of the immune response, is extremely important for human health. Dysfunction of the gut microbiota leads to the production of pro-inflammatory mediators, and inflammatory changes are observed not only in the intestine but also systemically in the body, increasing the risk of carcinogenesis.
However, science has gone further in studying the remote influence of the microbiome on organs, and the latest research is dedicated to the relationship between gut bacteria and the functioning of the nervous system. In early 2013, Dr. E. Mayer from Los Angeles hypothesized about the influence of the human gastrointestinal tract on brain development during growth through the gut microbiota. This influence affects the mood, behavioral reactions, and sensations of adults.
“These phenomena provide a completely new perspective on the functioning of the brain and, possibly, its disorders,” emphasizes Mayer (3). To confirm his assumptions, he began a study in which he used MRI to scan the brains of volunteers to study their functioning, and then compared the structure and activity of their brains with the types of bacteria detected in their feces using polymerase chain reaction (PCR). Currently, data from 60 volunteers have been obtained, allowing for some conclusions to be drawn. In particular, Mayer points out that the connection between different brain regions varies among individuals depending on the predominant type of gut bacteria they have.
Therefore, it can be assumed that a specific combination of bacteria may be responsible for influencing specific neural circuits and connections in the brain, and possibly even at lower levels of the nervous system. These data have not been proven to date, and research is ongoing.
However, Mayer is not alone in his assumptions. Most scientists interested in this issue conduct research on mice. In 2011, P. Bercik et al. (8) conducted a study on mice raised in special environments without exposure to specific infectious agents (specific pathogen-free – SPF) and mice raised in completely sterile conditions. Non-absorbable antimicrobial agents (neomycin, bacitracin, and pimaricin) were added to the drinking water of the animals for 7 days. Then, the mice raised in sterile conditions were colonized with microbiota from the SPF group of mice, and their behavior was studied using specific animal tests.
The composition of the gut microbiota was studied through sequencing. After euthanizing the animals, samples of the intestines were taken for histological examination, determination of myeloperoxidase levels, cytokines, as well as measurement of serotonin, norepinephrine, dopamine, and brain-derived neurotrophic factor (BDNF) produced by the brain. The administration of antibiotics to SPF mice led to temporary changes in the microbiome composition, increased exploratory behavior in animals, and increased BDNF expression in the hippocampus. These changes were observed regardless of the inflammatory activity of the body, levels of gastrointestinal neurotransmitters, and the influence of the sympathetic nervous system. The intraperitoneal administration of antibiotics or the oral administration of antibiotics to sterile mice did not lead to such changes.
However, perhaps the most surprising finding was regarding the introduction of microbiota from SPF mice to sterile mice. Animals that were colonized with foreign gut microbiota showed increased exploratory behavior, increased levels of BDNF in the hippocampus. These results confirmed the assumption of biochemical connections between the gut and the brain, regardless of the autonomic nervous system.
Therefore, the disruption of gut microbiota composition may be responsible for changes in psychological state and human behavior (8).
Animal studies have been further continued by S.M. Collins et al. (9), who showed that the same changes in brain biochemistry are observed in mice with fecal transplantation, and their behavior also changes depending on the donor. When microbiota from a group of mice that exhibit calmer behavior in stressful situations was introduced through fecal transplantation, initially anxious recipient mice also began to show more courage and less anxiety in performing tasks. Considering the fact that the method of microbiota transplantation through fecal transplantation is currently applicable to humans in cases of refractory Clostridium difficile infection, in some cases of inflammatory bowel diseases, and even diabetes, careful selection of donors for transplantation is necessary, with the absence of psychological disorders.
The latest study, published in early December 2013, reports on the connection between gut microbiota disorders and the presence of developmental delay syndrome, including autism. For the experiment, mice were selected whose mothers had changes in the microbiome, increased gut permeability, and immune activation. Offspring of such mothers, who suffered from developmental delay, as determined by observing individuals and conducting experiments on cognitive functions, were orally given a probiotic containing Bacteroides fragilis. As a result, normalization of gut barrier permeability, microbiome, improvement in communicative, stereotypical, sensorimotor behavioral skills, and greater resilience to stress were observed (1,3).
Research on the relationship between brain functioning and microbiome changes is gradually transitioning to studying these data in humans. In his study, Dinan TG et al. (10) suggested a connection between changes in gut microbiota and the presence of depression, as this psychological disorder is often observed in patients with gastrointestinal diseases. In conclusion, he acknowledges that there is insufficient data for an objective assessment of this relationship, and additional research is needed.
Thus, the discovery of a close connection between microbiome changes and animal behavior, which is likely to be proven in future studies on humans, leads us to a new understanding of metabolic processes in the body, in which the gut microbiota plays a significant role. Therefore, new therapeutic approaches for the treatment of both gastrointestinal diseases and mental disorders may be possible.
Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell, 05 December 2013
Sara Reardon. Bacterium can reverse autism-like behaviour in mice. Nature News. December 2013
Stein et al. Gut Bacteria Might Guide The Workings Of Our Minds. November 18, 2013
Bultman SJ. Emerging roles of the microbiome in cancer.Carcinogenesis. 2013 Dec 3.
Duseja A, Chawla YK. Obesity and NAFLD: The Role of Bacteria and Microbiota.Clin Liver Dis. 2014 Feb;18(1):59-71
Bonfrate L, Tack J, Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options. Scand J Gastroenterol. 2013 Sep;48(9):995-1009.
Shim JO.Gut Microbiota in Inflammatory Bowel Disease.Pediatr Gastroenterol Hepatol Nutr. 2013 Mar;16(1):17-21
Bercik et al. The Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice. Gastroenterology, Volume 141, Issue 2 , Pages 599-609.e3, August 2011
M. Collins et al. The adoptive transfer of behavioral phenotype via the intestinal microbiota: experimental evidence and clinical implications. Current Opinion in Microbiology Volume 16, Issue 3, June 2013, Pages 240–245
Dinan TG, Cryan JF. Melancholic microbes: a link between gut microbiota and depression? Neurogastroenterol Motil. 2013 Sep;25(9):713-9
https://internist.ru/publications/detail/izmeneniya-kishechnoy-mikroflory-i–funkcionirovanie-golovnogo-mozga:-est-li-svyaz?/.
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