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Nutritional Psychiatry

On April 22, 2022, the authoritative journal Nature published a study entitled "The role of nutrition and its effects on the gut microbiome and the pathophysiology of mental disorders."

The effect of nutrition on the variety, and thus on the good functioning of the intestinal microbiome, is already known. The interaction of the brain with the intestinal microbiome is also known. Thus nutrition became a therapeutic approach that is the focus of Nutritional Psychiatry.Nutritional Psychiatry is a relatively new field of research that developed from ground-breaking preclinical observations and a series of large, cross-sectional, epidemiological studies linking nutrition to different aspects of mental health and from knowledge gained from microbiome science that provided a link between diet, microbial function and brain health.Converging results from these studies support a potential role of diet and a potential beneficial role of specific nutritional interventions in various brain disorders, including but not limited to depression, cognitive decline, Alzheimer's disease (AD), autism, and some forms of epilepsy. . A growing number of interventional and mechanistic studies have confirmed the beneficial effect of a mainly plant-based diet, high in fiber and polyphenols, on mental health.

There are several ways in which nutrition promotes healthy brain structure and function, including:• the reduction and prevention of metabolic endotoxemia,• the neuroactive metabolites and• the essential micronutrients

a. In metabolic endotoxemia there is the presence of endotoxins in the blood, which, if derived from rod-shaped gram-negative bacteria, can cause hemorrhage, kidney necrosis, and shock.A number of preclinical and clinical studies have shown a relationship between the Standard American Diet (SAD) and an increase in markers of metabolic endotoxemia. Metabolic endotoxemia has been shown to result from a disrupted intestinal barrier ("leaky gut"). The increase of microbial classes with anti-inflammatory function, such as Faecalibacterium prausnitzii (F. prausnitzii), Eubacterium rectale (E. rectale), E. hallii and Ruminococcus bromii (R. bromii), contributes to the reduction of metabolic endotoxemia. Dietary factors that increase the relative abundance of these anti-inflammatory and other health-promoting bacteria include prebiotics such as oligosaccharides and polyphenols, some of which have prebiotic activity.If supported by controlled longitudinal intervention studies, such a nutritional approach combined with pharmacological and behavioral interventions promises significant results as a new therapeutic integrated approach for psychiatric disorders, using the knowledge discovered in the new field of Nutritional Psychiatry.b. A healthy diet can alter the synthesis and secretion of neuroactive metabolites by gut microbes, which affects brain function and health. As recently discovered , 95% of the body's serotonin is produced in the gut by enterochromaffin cells (ECC) and enteric nerve cells with the help of the microbiome. The gut microbiome influences serotonin production and secretion as a direct result of the food we eat (in particular the amount of tryptophan Trp), as diet modulates microbial composition. A higher Trp concentration in the gut leads to increased serotonin synthesis in ECCs. In a rodent study, it was found that mice with no gut microbiome had only half the amount of circulating serotonin compared to mice with a normal microbiome. Stimulation of ECCs by microbes or intestinal contents moving through the gastrointestinal tract triggers serotonin secretion at vagal sensory nerve endings and into the gut circulation and lumen. This stimulation of the vagus nerve can lead to signal relay in areas of the brain that regulate emotions. In the CNS, serotonin produced and stored in the rapha nuclei as well as vagal signals produced by serotonin release from ECCs are crucial for the regulation of sleep, appetite, pain sensitivity and disposition.c. Specific micronutrients such as omega-3 fatty acids and zinc may have a significant effect on brain development and function, independent of the gut microbiome. . Nutrients derived 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 for example neurotransmitter synthesis, myelination, cell signaling and metabolic pathways. Some specific nutrients have been intensively studied for their antidepressant effects, such as omega-3 fatty acids, folate, s-adenosyl-methionine, inositol, and vitamins B3, B6, and C, and may even be beneficial. if they act in addition to a healthy diet for the gut. A high ratio of omega-6 to omega-3 fatty acids can contribute to a pro-inflammatory state. In addition, low consumption of omega-3 fatty acids is reflected in mental illnesses such as depression.

In summary, a healthy diet rich in fiber, polyphenols, and micronutrients has been shown to positively influence gut microbial composition, reduce metabolic endotoxemia and neuroinflammation, and has been associated with improvements in brain health. Fiber has been associated with improved brain health and function in a variety of small-scale observational and interventional studies. The production and release of serotonin in the enteric nervous system is also greatly influenced by dietary choices, with the amounts of complex carbohydrates and tryptophan in the diet being the most important factors. Certain dietary micronutrients such as zinc, omega-3 fatty acids, folate and B vitamins may further affect brain development and function, a deficiency of which may lead to intellectual dysfunction and contribute to development of brain disorders.

Nutrition and depressionThere have been a number of recent studies showing that depressed patients have an altered gut microbiome (dysbiosis) compared to healthy controls, although the nature of the dysbiosis in each study varies, no consistent microbial biomarker has been identified, and causality between of gut dysbiosis and clinical symptoms of depression has not been established. A recent large faecal microbiome population study using data from the Flemish Gut Flora Project investigated the association between gut microbiome composition, depressive symptoms and quality of life indicators. The study found a negative correlation between measures of physical function and the Flavonifractor bacterial species. Coprococcus and Dialister bacterial species were found to be positively associated with quality of life and depletion in untreated depression. Participants with low Bacteroides relative abundance showed lower quality of life outcomes and a higher prevalence of depression. In addition, GABA and Tryp metabolism pathways were enriched in gut health-related microbiota, indicating a potential role of gut microbes in these pathways.Several studies have also shown that transferring the microbiome of a depressed individual to a healthy rodent (with no or suppressed gut microbiota) can induce depressive behaviors in the recipient mouse, suggesting the possibility of a causal role for the microbiome in the pathophysiology of depression. Given the significant impact of diet on the gut microbiome and the association of gut microbiome changes with depression-like behaviors, diet has emerged as a potential treatment strategy for depression.

Nutrition and Alzheimer's (AD)Alzheimer's disease (AD) is a progressive neurodegenerative disease that currently affects over 40 million people worldwide. The disease is characterized by memory loss and loss of executive function of the brain and can be accompanied by depression, anxiety and insomnia.There are several theories about the biochemical mechanisms underlying AD. Biomarkers for AD include the protein aggregates amyloid-beta (Aβ) and tau.Neuroinflammation as a precursor to cognitive impairment, which also depends on gut microbiome composition, has previously been associated with AD.AD patients have been found to exhibit reduced levels of systemic primary bile acids and enhanced levels of discrete secondary bile acids (the product of gut microbial metabolism) compared to healthy controls, which are directly related to impairments in cognitive function and glucose metabolism. brain. As bile acid synthesis is highly dependent on dietary factors and as secondary bile is produced exclusively by certain gut microbes, these findings suggest a possible role of diet and the gut microbiome in the observed changes in the ratio between primary and secondary bile acids . Secondary bile acid levels were associated with the progression of AD symptoms from mild to severe, with higher secondary bile acid levels being associated with worse cognitive function.In summary, evidence from preclinical, epidemiological, and a limited number of intervention studies supports the idea that a plant-based diet, such as the Mediterranean diet, helps improve cognitive function and reduce cognitive decline. These clinical benefits are related to a reduction in the levels of certain secondary bile acids, changes in brain structure, and positive changes in gut microbial composition.

Nutrition and autismAutism is characterized by a disorder of social communication and persistent repetitive behavior that is present in early development and significantly interferes with proper social functioning. Over the past decade and a half, the prevalence of autism has increased dramatically and now affects one in 54 children in the United States. Autism is often a comorbid condition with gastrointestinal symptoms, anxiety and immune dysfunction. Gastrointestinal symptoms often associated with autism include diarrhea, abdominal pain and discomfort, gastric reflux, and changes in bowel habits.As the risk genes that predispose to the development of autism have not changed over the past decades, various environmental risk factors, including diet and environmental toxins, have been implicated in its etiology. Several preclinical and clinical studies have found increased levels of inflammatory markers in the systemic circulation of autistic subjects compared to neurotypical controls, such as increased IL-1B and increased systemic TNF-alpha. Evidence for increased intestinal permeability has been reported in postmortem analysis of individuals with autism. These observations together with the common comorbidity of gastrointestinal symptoms and anxiety strongly suggest that gut dysbiosis may be part of the underlying pathophysiology of autism.A number of clinical studies are consistent with preclinical findings in demonstrating altered gut microbial composition and function in autistic patients, suggesting a potential role of the gut microbiome in the pathophysiology of autism.Taken together, these studies suggest that the core symptoms of autism as well as co-morbidities can be improved through comprehensive nutritional therapeutic interventions, the clear cause of which is yet to be identified and may include, but is not limited to, changes in the gut microbiome.Microbial Transfer Therapy (MTT) has emerged as a promising therapeutic approach for autistic patients, where a graft of microbes from a healthy donor is introduced into the patient. A study of autistic children treated with MTT found a significant sustained reduction in both gastrointestinal and autism symptoms and confirmed favorable changes in the abundance of certain beneficial bacterial taxa, including Bifidobacteria, Prevotella and Desulfovibrio. These results strongly support the view that the gut microbiome plays a pathophysiological role in autism.

Ketogenic diet in epilepsyAlthough epilepsy is a treatable condition with a prevalence of 1–3%, 30% of patients continue to have drug-resistant epilepsy (DRE) or recurrent seizure activity despite taking multiple antiepileptic drugs. The pathophysiology is not fully elucidated, but intestinal dysbiosis has been implicated, thus making the ketogenic diet a potential treatment that may exert antiepileptic effects due to changes in the intestinal microbiota. A landmark study in mouse models of epilepsy showed that a ketogenic diet protected against refractory seizures only in mice colonized with a specific gut microbiome compared to mice treated with antibiotics. The underlying mechanism involved a change in microbial abundance, leading to a decrease in γ-aminobutyrate (GABA) synthesis in the periphery while increasing GABA in the CNS to exert anticonvulsant effects.Emerging studies in epilepsy patients are beginning to elucidate the change in gut microbiota following ketogenic diet treatment. An initial meta-analysis of 10 RCTs on the ketogenic diet and drug-resistant epilepsy in children and one RCT in adults found evidence of a small reduction in seizures between the treated and untreated groups. However, the study was limited given the attrition rate and short follow-up time frame of 6 months or less.

Clinical implications and future directionsUntil an objective therapeutic benefit from specific dietary interventions is clearly established, practical implications are largely limited to the general recommendation of a healthy, mostly plant-based diet similar to the traditional Mediterranean diet, which has clearly been shown to be associated with increased abundance. diverse and species-rich gut microbiota with high abundance of anti-inflammatory SCFA producers, including F. prausnitzii, E. rectale, Roseburia and A. mucinophilia (Table 3). As discussed at length in this review, low-grade systemic immune activation due to increased gut permeability and decreased abundance of SCFA producers appears to be a common feature of many common chronic brain disorders, and an increase in the prevalence of butyrate-producing microbes in the gut should is a general therapeutic strategy. High-quality RCTs demonstrating benefits beyond following such a “microbiome-friendly” diet with supplementation in the form of pre-, pre-, or metabiotics (substances produced and released by the metabolic activity of the microbiome) are currently lacking available. although they may have small cumulative therapeutic effects.For example, intake of a consortium of butyrate producers can improve metabolic abnormalities and reduce systemic immune activation. Evaluation of the potential therapeutic benefit of fecal microbial grafts in brain disorders, mimicking such previously reported effects in animal models, has shown inconsistent and time-limited success, with the exception of the Autism Spectrum Disorder (ASD) study discussed earlier. However, confirmation of these findings in an RCT is necessary before recommendation as an effective treatment. Diagnostic testing of the gut microbiome to develop personalized nutritional approaches or to determine future risk for developing chronic brain disorders is in its early stages, and the benefits of such testing have not been demonstrated in prospective, longitudinal studies. The utility of basing individualized, specific dietary recommendations and supplements on stool microbiome assessments awaits objective evidence, although such tests, along with genetic risk factor assessment, may become a useful approach in the future. At present, individualizing a primarily plant-based diet to avoid gastrointestinal side effects, particularly bloating, gas, and abdominal discomfort in patients with psychiatric diagnoses and often comorbid gastrointestinal symptoms, is best done empirically. Patients should be started on a Mediterranean diet and encouraged to carefully identify foods that cause reproducible symptoms. Eliminating a small number of such foods will allow the patient to avoid gastrointestinal symptoms while following an optimal, personalized diet for brain health. Despite the limitation of currently available information, there are several recommendations supported by a body of preclinical and clinical evidence, including adherence to an anti-inflammatory, Mediterranean-type diet and the inclusion of nutritional counseling in addition to pharmacological and behavioral multidisciplinary treatment strategies.One of the main challenges of Nutritional Psychiatry Research is to gradually change the prevailing mindset shared by the majority of researchers and practitioners that psychiatric disorders are diseases of the brain and not of the gut and its microbiome. The education of mental health professionals about the critical role of nutrition and its impact on microbiome-brain-gut interactions, and the need for a multidisciplinary approach in this area is essential to making progress in this area of psychiatry.

NOTE TRANSLATOR ANTONI 1st : Dementia-Brain drainConsidering the annual cost of dementia is US$290 billion and after 146 failed trials, it is almost laughable that we are still trying to develop a drug. The fact is that diabetics are four times more likely to develop dementia than the general population. In addition, both forms of dementia (Alzheimer's disease and vascular dementia) are increased in people with diabetes—because insulin resistance affects the brain.New research shows that sugar consumption is associated with the development of Alzheimer's disease. Fructose appears to alter mitochondrial function in the brain, reducing energy production, which puts recognized neuronal proteins amyloid and tau at risk of accumulating, forming the classic neurofibrillary tangles of Alzheimer's. A refined eating pattern has been shown to be predictive of future Alzheimer's, although no one has yet proven that switching to real food reduces the risk.NOTE TRANSLATED 2ndDepression—the Moody BluesInsulin resistance has been shown to be a primary cause of clinical depression in humans. Sugar is a specific factor in insulin resistance and a cause of depression in both rats and humans. So it should come as no surpriseto anyone that two studies, one in Europe and one in China, have shown that eating highly processed foods is associated with depression in humans.The foods that cause metabolic syndrome are the ones most clearly associated with the foods people eat—processed carbohydrates and sugar.The question is whether depression drives dietary choices, which then drive metabolic syndrome. Or food choices drive metabolismsyndrome, which then leads to depression? What is the cause and what is the effect? We still don't know. But what we do know is that many people can avoid both their metabolic disease and depression by switching to a Mediterranean diet. The fact that your food choices canlift your mood certainly supports that food is a driver, although many changes in our society are linked to depression and other mood disorders.


Antonis Kayiorga, Biochemist


Metabolical, Robert Lustig.

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