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Evolution of the Human Diet and Its Impact on Gut Microbiota, Immune Responses, and Brain Health.
González Olmo, BM, Butler, MJ, Barrientos, RM
Nutrients. 2021;13(1)
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One explanation for the increased prevalence in chronic disease and mental illness is from the evolutionary perspective. This suggests the rapid shift in diet towards processed foods in the past 200 years has not allowed for sufficient adaptation of the gut microbiome. The gut microbiome plays an important role in the digestive, immune and nervous systems via the gut-brain axis, and may be a key factor in modulating inflammation and disease. The aim of this review is to discuss how what we eat affects the immune system and impacts our brain health. The literature currently shows significant associations between the Western diet and its impact on the health of the gut microbiome and the brain. Increased intake of saturated fats, refined carbohydrates and sugar, coupled with a reduction in fiber, negatively impacts the digestive system and elicits an immune response. This response can lead to neuroinflammation, which is now found to be associated with deficits in learning and memory, as well as increased rates of neurodegenerative disease and depression. Based on the existing literature, the authors conclude the human gut microbiome has not had sufficient time to adapt to many modern foods, thus leading to inflammation and disease. The authors recommend that a diet composed of natural whole foods with minimal processing can help prevent and alleviate some of the burden caused by chronic disease, and suggest future studies focus on improving techniques to evaluate neuroinflammation in humans.
Abstract
The relatively rapid shift from consuming preagricultural wild foods for thousands of years, to consuming postindustrial semi-processed and ultra-processed foods endemic of the Western world less than 200 years ago did not allow for evolutionary adaptation of the commensal microbial species that inhabit the human gastrointestinal (GI) tract, and this has significantly impacted gut health. The human gut microbiota, the diverse and dynamic population of microbes, has been demonstrated to have extensive and important interactions with the digestive, immune, and nervous systems. Western diet-induced dysbiosis of the gut microbiota has been shown to negatively impact human digestive physiology, to have pathogenic effects on the immune system, and, in turn, cause exaggerated neuroinflammation. Given the tremendous amount of evidence linking neuroinflammation with neural dysfunction, it is no surprise that the Western diet has been implicated in the development of many diseases and disorders of the brain, including memory impairments, neurodegenerative disorders, and depression. In this review, we discuss each of these concepts to understand how what we eat can lead to cognitive and psychiatric diseases.
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Gluten and FODMAPs Relationship with Mental Disorders: Systematic Review.
Aranburu, E, Matias, S, Simón, E, Larretxi, I, Martínez, O, Bustamante, MÁ, Fernández-Gil, MDP, Miranda, J
Nutrients. 2021;13(6)
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There is growing evidence that gluten and FODMAPs, such as fermentable oligosaccharides, disaccharides, monosaccharides and polyols, can cause gastrointestinal symptoms, inflammation, and immune responses in patients with celiac disease and irritable bowel syndrome. In addition, a high intake of gluten and FODMAPs may also be associated with neurological and psychiatric disorders. Thirteen studies were included in this systematic review to examine the relationship between gluten and FODMAP consumption and illnesses affecting the central nervous system. In addition, the studies examined the effects of potential dietary strategies that consider gluten and FODMAP intake on mental disorders, anxiety, depression, schizophrenia, Alzheimer’s disease, and autism spectrum disorders. Several possible mechanisms identified in this systematic review could contribute to neurological and psychiatric disorders, including the release of proinflammatory cytokines, immune responses, gut dysbiosis, intestinal permeability, and interactions between the gut-brain axis. In patients with fibromyalgia, celiac disease, and irritable bowel syndrome, avoiding or limiting gluten may reduce depression, anxiety, and cognitive impairment. However, the effects of a low-FODMAP diet on the central nervous system are inconclusive. There is some evidence that gluten-free diets can improve cognition in schizophrenia patients. In addition, those with autism spectrum disorders may benefit from a gluten-free diet and a low-FODMAP diet. Further robust research is required to evaluate the beneficial effects of interventions that avoid or restrict the consumption of foods high in FODMAPs and gluten. However, healthcare professionals can use the results of this systematic review to understand the potential benefits of therapeutic interventions that consider the intake of FODMAPs and gluten on illnesses affecting the central nervous system and their possible mechanisms of action.
Abstract
Nowadays, gluten and FODMAP food components (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) are increasingly studied due to their possible relation with extraintestinal-associated conditions. In recent years, gluten-free diets (GFD) and low-FODMAP diets (LFD) are becoming more popular not only in order to avoid the food components that cause intolerances or allergies in some people, but also due to the direct influence of marketing movements or diet trends on feeding habits. Likewise, neurological and psychiatric diseases are currently of increasing importance in developed countries. For this reason, a bibliographic systematic review has been carried out to analyse whether there is a pathophysiological relationship between the dietary intake of gluten or FODMAPs with mental disorders. This review collects 13 clinical and randomized controlled trials, based on the PRISMA statement, which have been published in the last ten years. Based on these results, limiting or ruling out gluten or FODMAPs in the diet might be beneficial for symptoms such as depression, anxiety (7 out of 7 articles found any positive effect), or cognition deficiency (improvements in several cognition test measurements in one trial), and to a lesser extent for schizophrenia and the autism spectrum. Nevertheless, further studies are needed to obtain completely reliable conclusions.
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Gut microbial metabolites in depression: understanding the biochemical mechanisms.
Caspani, G, Kennedy, S, Foster, JA, Swann, J
Microbial cell (Graz, Austria). 2019;6(10):454-481
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Major depressive disorder is a leading cause of disability and is linked to shortened life expectancy and suicide. Despite its prevalence, for near to a third of patients, long-term treatment options are ineffective. In addition to the primary presentation of persistent low mood, other emotional and physiological symptoms, researchers have also identified alterations in metabolism, hormones and the immune system. Furthermore, increasing evidence suggests that depression and depressive behaviour is also influenced by divergences in gut health and gut bacteria composition. With insights from animal and human research, this review highlights how the gut and gut bacteria-derived metabolites can directly or indirectly influence mood. Described are the pathways of how the gut and its microorganism communicate with the brain, the essential role the immune system has as part of the gut-brain communication, and the impact of low-grade, chronic inflammation on neurofunction. Comprehensive summaries are dedicated to how several metabolites or by-products from gut bacteria can influence the nervous system and gene expression in relation to depression. These include substances like neurotransmitters, short-chain fatty acids, tryptophan metabolites, lactate, bile acids, choline metabolites and folate. This article yields a detailed overview of how gut health and microbiota can influence neurofunction and mental health. The authors promote the idea of the gut as a suitable target for the management of depressive disorders, whilst also eluding to the current limitations and need for further research.
Abstract
Gastrointestinal and central function are intrinsically connected by the gut microbiota, an ecosystem that has co-evolved with the host to expand its biotransformational capabilities and interact with host physiological processes by means of its metabolic products. Abnormalities in this microbiota-gut-brain axis have emerged as a key component in the pathophysiology of depression, leading to more research attempting to understand the neuroactive potential of the products of gut microbial metabolism. This review explores the potential for the gut microbiota to contribute to depression and focuses on the role that microbially-derived molecules - neurotransmitters, short-chain fatty acids, indoles, bile acids, choline metabolites, lactate and vitamins - play in the context of emotional behavior. The future of gut-brain axis research lies is moving away from association, towards the mechanisms underlying the relationship between the gut bacteria and depressive behavior. We propose that direct and indirect mechanisms exist through which gut microbial metabolites affect depressive behavior: these include (i) direct stimulation of central receptors, (ii) peripheral stimulation of neural, endocrine, and immune mediators, and (iii) epigenetic regulation of histone acetylation and DNA methylation. Elucidating these mechanisms is essential to expand our understanding of the etiology of depression, and to develop new strategies to harness the beneficial psychotropic effects of these molecules. Overall, the review highlights the potential for dietary interventions to represent such novel therapeutic strategies for major depressive disorder.
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Small talk: microbial metabolites involved in the signaling from microbiota to brain.
Caspani, G, Swann, J
Current opinion in pharmacology. 2019;48:99-106
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The gut-brain axis (GBA) is the communication network between the gastrointestinal tract and the central nervous system. An array of gut bacteria-derived metabolites mediates this interaction between the gastrointestinal system and the brain, influencing physiological and pathological processes in direct and indirect ways. Thus a variation in the gut microbiome can alter the functional capacity and output of the gut-brain-communication. In this review, the authors summarise key bacterial metabolites from the gut and their effect on the brain. Addressed are short-chain fatty acids, their impact on gut and brain barrier integrity, their role in appetite regulation, and their association with anxiety and depressive disorders amongst other aspects. Secondly, bile acids, which are processed by the microbiome, can activate several receptors. And thus divergence gut bacteria can alter the composition of bile acids and change their signalling capacity. Bile acids can also directly modify gut and blood-brain barrier function and may carry a signalling role in the brain. A few neurotransmitters are covered in this article, as several types of gut bacteria synthesize neurotransmitters, such as serotonin and dopamine. Though, it is uncertain whether all gut-derived neurotransmitters can reach the brain. However, certain GABA-producing bacteria have been shown to elicit higher GABA levels in the brain. The microbiota can also be involved with the conversion of neurotransmitters such as dopamine. The final section briefly capture the evidence of other brain health-relevant molecules derived from the intestinal microbiota, including Lipopolysaccharides, choline, lactate and B-Vitamins. This review yields a short and comprehensive summary highlighting the many ways the gut can influence brain function and health and could be of interest to those providing mental health support in light of gut function.
Abstract
The wealth of biotransformational capabilities encoded in the microbiome expose the host to an array of bioactive xenobiotic products. Several of these metabolites participate in the communication between the gastrointestinal tract and the central nervous system and have potential to modulate central physiological and pathological processes. This biochemical interplay can occur through various direct and indirect mechanisms. These include binding to host receptors in the brain, stimulation of the vagus nerve in the gut, alteration of central neurotransmission, and modulation of neuroinflammation. Here, the potential for short chain fatty acids, bile acids, neurotransmitters and other bioactive products of the microbiome to participate in the gut-brain axis will be reviewed.
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Chronic Food Antigen-specific IgG-mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder.
Tao, R, Fu, Z, Xiao, L
Genomics, proteomics & bioinformatics. 2019;17(2):183-189
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The prevalence of major depressive disorder (MDD) among adolescents has been on the rise recently. A high level of systemic low-grade inflammation is found in the serum of MDD adults, which is believed to interfere with neurotransmitter metabolism, resulting in symptoms of depression. Furthermore, disruption of the blood-brain barrier may inhibit neurotransmitter metabolism. One hundred and eighty-four adolescents with moderate MDD were evaluated against the same number of healthy controls to determine their serum levels of markers of inflammation, homocysteine, food sensitivity, histamine, and histamine metabolism. The study found that histamine levels and food antigen-specific antibodies in MDD adolescent patients were significantly higher than those in the control group. Increasing histamine levels, food-specific IgG levels, and S100 calcium-binding protein B levels suggest blood-brain barrier leakage may contribute to adolescent depression. There is still much to be learned about the pathophysiology of MDD, and further studies are needed to elucidate the mechanisms involved. The results of this study can be used by healthcare professionals to understand the role of histamine and food sensitivities in the development of adolescent depression rather than low-grade inflammation.
Abstract
Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
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Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.
Patrick, RP
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019;33(2):1554-1564
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Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive memory loss, spatial disorientation, cognitive impairment and behavioural changes. Ageing is the main risk factor for AD, with approximately one-third of Americans over the age of 85 being affected by the condition. The APOE gene provides instructions for making the apolipoprotein E family of proteins that are involved in fat metabolism and cholesterol transport. There are three different variants of this gene, one inherited from each parent. The variant called APOE4 is thought to increase AD risk from 2-3-fold (one inherited copy) to as much as 15-fold (two inherited copies), compared to individuals who do not carry this variant. The omega-3 oil docosahexaenoic acid (DHA) is an essential fatty acid, which comprises approximately 30% of the fats found in the human brain. Low levels of DHA in the brain increase the risk of developing AD, while normal and high levels may prevent the condition and ameliorate symptoms. This review paper brings together several lines of evidence on why individuals with the APOE4 gene variant don’t respond well to DHA supplementation but experience positive effects from dietary intake of DHA. The author suggests that this is due to the different forms of DHA found in dietary and supplemental sources. Some of the DHA present in fish and seafood is in phospholipid form, which is metabolised into lysophosphatidylcholine DHA (DHA-lysoPC) in the body. In contrast, fish oil supplements contain no DHA in phospholipid form, but in other forms that are mostly metabolised to free DHA. This paper puts forward an argument that, due to the breakdown of the integrity of the blood-brain barrier, APOE4 carriers have impaired brain transport of free DHA but not DHA-lysoPC. The author concludes that dietary sources that contain high amounts of DHA in phospholipid form, such as fish and fish roe may help increase plasma levels of DHA-lysoPC, which may be better transported to the brains of APOE4 carriers. She also highlights the pressing need for future clinical trials to evaluate the effects of omega-3 oils in phospholipid form on the cognitive function of APOE4 carriers with AD.
Abstract
Dietary and supplemental intake of the ω-3 fatty acid docosahexaenoic acid (DHA) reduces risk of Alzheimer's disease (AD) and ameliorates symptoms. The apolipoprotein E ( APOE) 4 allele is the strongest risk factor for sporadic AD, exclusive of age. APOE4 carriers respond well to the DHA present in fish but do not respond as well to dietary supplements. The mechanisms behind this varied response remain unknown. I posit that the difference is that fish contain DHA in phospholipid form, whereas fish oil supplements do not. This influences whether DHA is metabolized to nonesterified DHA (free DHA) or a phospholipid form called lysophosphatidylcholine DHA (DHA-lysoPC). Free DHA is transported across the outer membrane leaflet of the blood-brain barrier (BBB) via passive diffusion, and DHA-lysoPC is transported across the inner membrane leaflet of the BBB via the major facilitator superfamily domain-containing protein 2A. I propose that APOE4 carriers have impaired brain transport of free DHA but not of DHA-lysoPC, as a consequence of a breakdown in the outer membrane leaflet of the BBB, putting them at increased risk for AD. Dietary sources of DHA in phospholipid form may provide a means to increase plasma levels of DHA-lysoPC, thereby decreasing the risk of AD.-Patrick, R. P. Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease.