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Although psychiatric disorders are primarily considered brain diseases, the influence of the digestive system on brain health and the occurrence of mental disorders was first mentioned in traditional Chinese medicine, Ayurveda, and Hippocratic medicine. As nutrition has a great influence on the microbiological composition and function of the human intestine, the idea that nutrition can play a causal role in changes in the intestinal microbiome with an impact on human emotional and cognitive functions has become an exciting research topic in psychiatry, and the term nutritional psychiatry has been proposed.
Lack of macro- and micronutrients in early life can compromise the development of brain function. Previous research on the impact of nutrition on brain development has focused mainly on amino acids and micronutrients that are absorbed in the proximal small intestine. However, large molecules that are not absorbed in this way are gaining more and more importance. Their absorption depends on the metabolism of intestinal microbiota in the distal small intestine and large intestine. So the health benefit of these molecules depends on the composition of the intestinal microbiome. 
The so-called nutritional psychiatry developed from preclinical observations and epidemiological studies in which the connection between nutrition and mental health was determined. The results of these studies support the role of nutrition and the possibility of a beneficial role of dietary changes in various mental disorders. This includes Alzheimer's disease, depression, cognitive decline, and epilepsy, but the possibilities do not end there. Some research also points to the potential of dietary changes in autism, Parkinson's disease, anxiety, etc. 
There are three pathways of communication between the gut microbiome and the brain. These are the neural, immunoregulatory, and endocrine pathways. The central nervous system directly influences the composition and function of the microbiome through the autonomic nervous system, or indirectly through the regulation of gastrointestinal (GI) motility and transit, mucus secretion and intestinal barrier permeability, and luminal release of neurotransmitters. 
Neuroendocrine communication channel
In preclinical studies, it has been shown that many microbes can produce metabolites (from body secretions, food components, or chemical substances) that affect brain function. One such process is the conversion of the amino acid tryptophan into metabolites that play an important role in neuroendocrine signaling by neuroimmune mechanisms. Tryptophan is a precursor of serotonin and other important metabolites. .
About 95% of the serotonin in the body is produced and stored in the ECC (enteroendocrine cells) and plays an important role in modulating the activity of the enteric nervous system and in signaling to the brain via different subtypes of vagal afferents that form synaptic contacts with the ECC. Microbial metabolites stimulate serotonin production and release by ECC. While serotonergic neurons located in the brainstem play an important role in the regulation of functions such as sleep, food intake, mood regulation, and pain, gut-based serotonin plays an important role in gastrointestinal motility and secretion .
Kynurenine is also an important Trp metabolite. In a rodent model of chronic variable stress, higher brain kynurenine concentrations were correlated with increased depression-like behavior. This behavior is reduced by the use of Lactobacillus, which regulates the synthesis of kynurenine. Kynurenine, which can cross the blood-brain barrier, has been shown to cause neuroinflammation and neurodegeneration, which has also been reported in Alzheimer's disease and depression .
Another type of Trp metabolites is indoles, which are produced exclusively by intestinal microbes since only certain microbes possess the enzyme tryptophanase necessary for their production from Trp. Although many indoles are known to positively affect both systemic and intestinal homeostasis, preclinical studies have shown that some indole metabolites may also have negative effects on brain health, such as inducing depression-like behavior. Indoles are precursor molecules for many compounds critical to brain health and function. They have been detected in the GI tract, brain, and systemic circulation. One such metabolite, indoxyl sulfate, may play a role in the pathophysiology of several brain disorders, including Alzheimer's disease and depression. 
Interactions of gut microbes with dietary tryptophan that lead to the generation of multiple neuroactive metabolites, some of which have been implicated in several brain disorders, clearly demonstrate the intricate relationship between diet, the gut, and certain gut microbes and brain disease.
The immune communication channel
There is a close link between immune activation in the gut and neuroinflammation in the brain, as the gut microbiome can directly influence the maturation and function of microglia in the CNS as part of immunoregulatory pathways. Microglia make up the majority of immune cells in the brain, and gut bacteria play an important role in their proper functioning. Dysregulation of microglia and gut microbial dysbiosis has been implicated in several psychiatric disorders, such as anxiety, depression, neurodegenerative disorders, such as Parkinson's and multiple sclerosis, and neurodevelopmental disorders, such as ASD. 
The close relationship between inflammatory signals originating from the gut in response to certain diets and the key roles of the gut microbiota in generating both pro- and anti-inflammatory signals highlight the important interactions between diet, the gut microbiome, and brain disease.
There are several ways in which nutrition promotes healthy brain structure and function, including the reduction and prevention of metabolic endotoxemia, neuroactive metabolites, and essential micronutrients.
Low-grade inflammation due to increased circulating endotoxins is called metabolic endotoxemia. Dietary factors that increase the relative abundance of these anti-inflammatory and other health-promoting bacteria include prebiotics. Several clinical studies have shown the beneficial effects of a diet rich in prebiotics on the diversity and richness of the gut microbiome, and the reduction of systemic immune activation. Such Mediterranean-like diets can promote healthy brain function as demonstrated in a variety of dietary intervention trials in depression and cognitive decline .
Omega-3 fatty acids and zinc may have important effects on brain development and function independently of the gut microbiome. Nutrients obtained from the diet, such as vitamins, minerals, polyunsaturated fats, and amino acids, support healthy brain function. Many of these nutrients serve as cofactors for enzymes, supporting neurotransmitter synthesis, myelination, cell signaling, and metabolic pathways. Several specific nutrients have been extensively studied for their antidepressant effects, such as omega-3 fatty acids, folic acid, s-adenosyl-methionine, inositol, and vitamins B3, B6, and C, and may even be beneficial when added to supplements, but only if as a supplement to a gut-healthy diet. Furthermore, low omega-3 fatty acid intake has been linked to mental illnesses such as depression.
In summary, a healthy diet rich in fiber, polyphenols, and micronutrients has been shown to have a positive effect on gut microbiota, reduce metabolic endotoxemia and neuroinflammation, and is associated with improved brain health. Fiber has been associated with improved health and brain function in several small observational and interventional studies .
Diet, the brain-gut-microbiome (BGM) system, and brain disorders.
In several psychiatric and neurological disorders, a connection between changes in diet and interaction of the BGM system has been observed.
Diet and depression
Recent studies show that patients with depressive disorders have an altered gut microbiome compared to healthy individuals. One study investigated the association between gut microbiota composition, depressive symptoms, and quality of life indicators. The study found that the bacterial species Flavonifractor is deficient in individuals with reduced physical functioning. The bacterial species Coprococcus and Dialister were positively associated with quality of life and are lacking in people with untreated depression. Participants with low Bacteroides levels showed a poorer quality of life and higher incidence of depression. 
Several mouse studies have shown that transferring the microbiome of a depressed individual to a healthy one can induce depressive behavior in the recipient. That indicates the possibility of a causative role of microbiota in the pathophysiology of depression. As a diet has an important influence on the gut microbiome, and changes in the gut microbiome have been linked to depression-like behaviors, the diet has emerged as a potential treatment strategy for depression. The study found evidence for a statistically significant relationship between unhealthy eating patterns and poorer mental health, as well as for quality nutrition and better mental health in children and adolescents. 
However, in cross-sectional studies, there are no conclusions about the relationship between diet and mental health. The reason can be that subjects with depressive disorders eat more unhealthy food to self-medicate. Another possible reason is the influence of early eating habits on brain development. There is evidence that nutrient-poor diets can lead to nutrient deficiencies, which are linked to mental health problems. Folate, zinc, and magnesium intakes are inversely associated with depressive disorders, while omega-3 fatty acids are inversely associated with anxiety disorders. 
Yet, several studies have confirmed a correlation between mental well-being and a healthy diet rich in fresh fruits, vegetables, and whole grains. The benefits of a plant-based diet in depression are anti-inflammatory effects due to increased production of short-chain fatty acids and polyphenols and improvement of intestinal permeability. That leads to a reduction in metabolic endotoxemia. Increased intake of omega-3 fatty acids and minerals can alleviate deficiencies in nutrients for mood and brain health. 
Diet and Alzheimer’s disease
Studies have pointed to a neural connection between the gut microbiome and areas of the brain affected by Alzheimer's disease.
Neuroinflammation, which precedes cognitive impairment and depends on the composition of the intestinal microbiome, is already associated with Alzheimer's disease. It has been shown that patients with this disease have reduced levels of systemic primary products of intestinal microbial metabolism and increased levels of various secondary products compared to healthy individuals, which is directly related to cognitive impairment and glucose mechanism in the brain. As bile acid synthesis is crucially dependent on dietary factors, and as secondary bile is generated by gut microbes, these findings suggest a possible role of diet and the gut microbiome in the observed changes in the relationship between primary and secondary products of gut microbial metabolism. Secondary levels were associated with the progression of mild-to-severe Alzheimer's disease symptoms and poorer cognitive function. 
Ketogenic diet and Alzheimer's disease
Clinical studies have shown a positive effect of the ketogenic diet on patients with AD or mild cognitive impairment. Preclinical findings from these studies indicated that diets that can induce high blood ketone levels may also improve cognition and memory in these patient groups. 
Diet and Autism
Autism spectrum disorder (ASD) is often combined with gastrointestinal symptoms, anxiety, and immune dysregulation. GI symptoms often associated with ASD include diarrhea, abdominal pain and discomfort, gastric reflux, and changes in bowel habits.
Several preclinical and clinical studies have revealed increased levels of inflammatory markers in the systemic circulation of individuals with ASD. Intestinal permeability has also been proven in these people. These observations, together with the common comorbidity of GI symptoms and anxiety, suggest that gut dysbiosis may be part of the underlying pathophysiology of ASD.
Several smaller studies have investigated nutrition as a treatment option for ASD. In one, 70 children with ASD participated, and the effect of a 12-month dietary intervention consisting of a gluten- and casein-free diet was examined. Improvement was found for 81% of participants after three months. 
Microbial transfer therapy has emerged as a promising treatment approach for patients with ASD. A transplant of microbiota from a healthy donor is inserted into the patient. A study with children with ASD who underwent this therapy found significant reductions in GI and ASD symptoms. Also, this study confirmed favorable changes in the abundance of beneficial bacterial strains, including Bifidobacteria, Prevotella, and Desulfovibrio. This study indirectly suggests that dietary manipulation of the gut microbiome may have a therapeutic effect mediated by gut microbes. 
Diet and Epilepsy
Intestinal dysbiosis can be included in the pathophysiology of epilepsy. That makes the ketogenic diet a potential therapy that may have antiepileptic effects. The study in mouse models of epilepsy showed that a ketogenic diet protected against refractory epileptic seizures only in mice colonized with a specific gut microbiota compared to mice treated with antibiotics. The underlying mechanism involved a change in microbial abundance, which led to a decrease in GABA synthesis in the periphery, while an increase in GABA in the CNS showed an anti-seizure effect. 
The study of 14 children with drug-resistant epilepsy and 30 healthy individuals showed that a week-long ketogenic diet led to a 50% reduction in seizure frequency in infants, which was associated with reduced levels of Proteobacteria and increased levels of beneficial strains of Bifidobacterium, Bacteroides and Prevotella compared to baseline, correlated with suppression of seizure activity. 
The results of studies examining the role of nutrition in improving psychiatric disorders remain mixed. However, one of the main challenges of nutritional psychiatry research is to gradually change the prevailing way of thinking that psychiatric disorders are diseases of the brain and do not involve the gut and its microbiome. Educating mental health professionals about the critical role of nutrition and its impact on brain-gut microbiome interactions is necessary to make progress in this area of psychiatry.
There is emerging evidence that diet has a major modulatory influence on brain-gut-microbiome (BGM) interactions with important implications for brain health and for several psychiatric disorders including depression.
Interested how changing you’d diet can improve your BGM and reduce symptoms such as fatigue, depression, and anxiety? Call CPC @ 561-531-7818 to make an appt with Jessica Coote, APRN, Weight Management And Holistic Approach Specialist.