Gut microbiota and brain functions
The Gastrointestinal tract (GIS) is the largest immune organ. Products related to GIS can be neuropatogenic. The potential mechanisms of the effect of microbiota on the central nervous system are summarized as follows: changes in microbial content, immune arousal, neural pathways, tryptophan metabolism, intestinal hormonal response, bacterial metabolites. As a result of fermentation of carbohydrate-weighted diets, short-chain fatty acids are formed and interfere with the systemic circulation, affecting brain function. The Nervus vagus, on the other hand, forms a direct connection between the brain and the stomach and intestines, such as a wide highway. Hormonal, neural and interestingly bacterial changes in the intestines are transmitted to the brain through the nervus vagus. Gut microbiota BDNF (brain-derived neurotrophic factor) has been shown to be effective on brain development and plasticity by secreting many neurotrophins and proteins, such as syniptophysin, PSD-95.
External factors, microbiota and brain
As can be seen in the image given on the left, external factors such as diet, stress, probiotics, antibiotics affect the microbiota, the microbiota affects our behavior in the brain. Advances in modern life, such as antimicrobial treatments, vaccination, intensive consumption of dezanfectan cleaning products, and dietary changes, have profound and lasting effects on the microbiome. Changes in bowel mikrobiyota Clostridium difficile infection, irritable bowel syndrome (IBS), pathogen colonization (e.g. vancomycin-resistant Enterococcus), autoimmune and allergic diseases, obesity and metabolic disorders, such as autism are the cause of neuropsychiatric disorders. Bacterial proteins with neuroactive properties (p-cresol and 4-methylphenol) can enter the systemic circulation through the violation of the integrity of the intestinal epithelial wall.
A large number of studies have been conducted on immune system problems in schizophrenia. It has been found that the incidence of rheumatoid arthritis in schizophrenics is low. Antigliadin antibodies and gluten sensitivity have been shown to be increased in schizophrenics. It has been shown that there is an association between nonchalant gluten sensitivity and diseases such as autism and schizophrenia. Casein antibodies also increased in schizophrenics. It has been noted that Casein IgG antibody height can be a predictor for schizophrenia and increases the risk of schizophrenia by 18%. Decreased production of BDNF and NMDA 2a was found in GF mice. Normal microbiome development is required to ensure proper expression of BDNF and NMDA receptors for stimulation of brain plasticity. Changing the microbiota can cause NMDA dysfunction in schizophrenia. The immune response from GIS to antigens that leak into the systemic circulation may be involved in the pathogenesis of schizophrenia. Numerous studies point to neuroinflammation through proinflammatory cytokines in the pathogenesis of schizophrenia. Minocycline, a second-generation tetracycline, has been shown to have anti-psychotic effects in rats, acting on additional treatment of schizophrenia and especially negative symptoms in treatment-resistant schizophrenia. The positive effect of an antibiotic on schizophrenia is a very interesting finding. There is no research on the effectiveness of probiotics in schizophrenia. Studies have focused more on the metabolic syndrome that accompanies schizophrenia. The effect of microbiota on schizophrenia has only been studied in one clinical study. In this study, which compared serological immune markers between schizophrenics, bipolar patients and the control group, it was found that microbial products participating in systemic circulation cause immune imbalances in schizophrenics.
Campylobacter jejuni has been shown to lead to anxiety-like behavior without immune response in mice given orally in subclinical doses. Experimentally elevated (HPA) axis response and depression in glucose-Fed (GF) mice can be reversed by administration of only a single bacterium, bifidobacterium infantis. Bifidobacterium infantis is predominately present in the newborn intestine and probiotic drugs. Due to its antidepressant effect, this bacterium has been described as “psychobiotic”. As a result of a 2010 experiment by Desbonnet and colleagues, it was stated that Bifidobacterium infantis causes relaxation in neural processes . The link between microbiota and anxiety-related behaviors in mice has been shown through many studies. Rats given Lactobacillus helveticus and Bifidobacteria longum for 14 days in one experiment scored low on anxiety tests. In a double-blind placebo-controlled and randomized parallel group study conducted by the same team on healthy volunteers, the subjects were L. for 30 days.helvetikus R0052 and B.he took longum or a placebo. Psychiatric parameters were evaluated with a saw. It was found that psychological stress levels decreased and urine free cortisol levels decreased in subjects who regularly took probiotics every day. In another experiment, a decrease in both anxiety and depression scores was found in mice given Lactobacillus rhamnosus for 28 days. The most striking results were determined by the following experiment; anxiety-like behavior obtained with a high-fat diet was prevented by giving Lactobacillus helveticus for 21 days, while no change in anxiety was achieved when the same application was performed in mice deprived of IL-10. This finding revealed the role of immune regulation in the intestinal brain axis. Administration of Lactobacillus farciminis has been shown to reduce the HPA axis response ( (ACTH), corticosteroid level, (CRH) levels) to stress in mice.
In clinical trials, the bacterioides family has been associated with depression. Serum IgM and anti-IGA lipopolysaccharide levels were increased. In healthy individuals, milk fermented with probiotic bacteria has a positive effect on emotional centers. The study by Tillisch and colleagues was the only study in which the relationship between probiotics and healthy brain function was examined using fMRG (functional magnetic resonance imaging). Berk and colleagues noted that depression has a chronic, low-level inflammatory condition, which may be associated with intestinal permeability disorder. The key role between unhealthy eating and depression is thought to be microbiota.
Autism Spectrum Disorder
It was found that neuroinflammatory markers increased in mice that exhibited autistic behavior with Prenatal valproic acid administration. These autistic behaviors have been treated with bacteroides fragilis.Intestinal permeability disorders have been repaired by bacteria through tight junction expression and cytokine production. High levels of 4 – ethylphenylsulfate, a bacterial metabolite, were found in serum in autistic mice. It has been observed that autistic behavior occurs when this substance is given to normal mice. Low in bifidobacter species in autistic children, height in lactobacillus species and height in bacteroides species were also found. As a result of a high-carbohydrate diet, there are also opinions that the production of short-chain fatty acids in the intestines increases, and by mixing them into the systemic circulation, it causes autistic behavior.
Irritable bowel syndrome (IBS)
Numerous studies in IBS have revealed the beneficial effects of probiotics. In a parallel-group placebo-controlled study, Bifidobacterium infanticide was shown to show marked improvement in gastrointestinal symptoms. This treatment effect is explained by the reduction of proinflammatory cytokines.
In mouse experiments, dietary style changes have been shown to affect learning and memory functions, leading to differentiation in gut microbiota diversity. It is not known whether cognitive dysfunction occurs directly or as a cause of anxiety.
Alcohol weakens the intestinal mucosa wall, facilitating the mixing of bacterial-derived lipopolysaccharides and peptidoglycans into the systemic circulation. These substances cling to the TLR-4 and TLR-2 receptors in mononuclear cells in the peripheral blood, causing the secretion of pro-inflammatory cytokines (IL-1beta, IL-8 and IL-18). A small number of studies have been conducted on microbiota and alcohol dependence. Chronic alcohol consumption has been found to increase IL levels by activating inflammatory processes. A correlation was found between these IL levels and alcohol consumption and alcohol craving levels. In their second study, the same team investigated the role of intestinal permeability in alcohol addiction. Bowel permeability was found to be proportional to the severity of alcohol dependence.
Obesity and Metabolic Disorders
Muccioli et al suggested that the gut microbiota interacts with cannabinoid receptors in the brainstem, specifically that Lactobacillius acidophilus stimulates the production of cannabinoid receptors, and thus this bacterium may have an association with obesity. In a mouse experiment, gaita was taken from mice on a high-fat diet and transplanted into the intestines of mice on a normal diet (Fecal Microbiota Transplantation, FMT). Impaired intestinal wall continuity, increased circulating endotoxins, increased TLR-2 and TLR-4 levels, increased neuroinflammation, impaired cerebrovascular homeostasis and behavioral changes were found in mice fed a Normal diet. An interesting finding is that the intestinal microbiota of the obese type causes immunological and behavioral changes before obesity occurs.
In a study by Morgan and colleagues, two groups of GF mice fed only a high-fat diet and a diet with 50 mg/kg of zapine added In addition to a high-fat diet were monitored for 7 weeks. No difference in weight gain was found between the two groups at the end of seven weeks. It has been concluded that in order for mice to have weight gain due to insulin, there must be an intestinal microbiota. In addition, according to feces microbiota analyses conducted before, during and after application, it was found that Olanzapine changes the bacterial flora in an obesogenic way. Perhaps the most interesting finding of the experiment is that it has been determined that amoxicillin has an antimicrobial (antibiotic) effect on the resident bacterial flora.
Treatment With Gut Microbiota Regulation
Prebiotic is defined as promoting the development of one intestinal micro-organism more than another, while probiotic is defined as taking a special micro-organism orally or rectally. It is estimated that there is an annual market of $ 1 billion in over-the-counter probiotics in the United States. Activated charcoal is used to treat poisoning caused after high-dose drug purchases. It binds to toxins, preventing their absorption from the intestines. Tablets and capsules are used to reduce diarrhea, indigestion and bloating complaints. It helps to relax GIS by binding to toxins released by the microbiota. FMT has been successfully applied since time immemorial to treat Clostridium difficile infection, IBS and inflammatory bowel diseases (ulcerative colitis and crohn’s disease). Recent studies on its effectiveness in the treatment of cardiometabolic and autoimmune disorders have increased. The Ideal approach should be to restore the microbiota with probiotics without the need for FMT.
The gut microbiota and the effects of bacteria on human health are likely to be the focus of attention in neuroscience over the next decade. There are also authors who present microorganisms as a new group of drugs called “psychomicrobiotics” in the treatment of psychiatric disorders . The intestinal brain axis is perhaps a missing link that will allow neuropsychiatric disorders to be fully understood and treated.