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Towards Tailored Gut Microbiome-Based and Dietary Interventions for Promoting the Development and Maintenance of a Healthy Brain.
Larroya, A, Pantoja, J, Codoñer-Franch, P, Cenit, MC
Frontiers in pediatrics. 2021;9:705859
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The cause of neurodevelopmental disorders (NDDs) is complex and multifactorial. Recent studies have indicated that early life disturbances of the gut microbiome can impact neurodevelopment, suggesting this critical window may play a key role in the prevention or progression of neurological disease. The growing field of personalized nutrition works on the basis of tailored dietary intervention strategies that consider individual variability based on genetics, diet, and the environment. The aim of this paper is to review the current evidence on the neurodevelopmental interaction between the gut microbiota, environment and host, and assess the efficacy of tailored, personalized nutrition interventions aimed at preventing or treating NDDs. The literature provides evidence that the gut microbiota is susceptible to influence by various factors early in life, and the health of the microbiome may modulate mental health consequences later in life. Additionally, key nutritional deficiencies and microbiome alterations have been linked to NDDs, suggesting potential markers that may lead to improved prevention and treatment. Based on the current literature, the authors emphasize the need for further research during the critical window of microbiome development in order to target the cause of neurodevelopmental impairments. They suggest these findings could help progress the field of Nutritional Psychiatry towards effective tailored nutrition and personalized medicine.
Abstract
Mental health is determined by a complex interplay between the Neurological Exposome and the Human Genome. Multiple genetic and non-genetic (exposome) factors interact early in life, modulating the risk of developing the most common complex neurodevelopmental disorders (NDDs), with potential long-term consequences on health. To date, the understating of the precise etiology underpinning these neurological alterations, and their clinical management pose a challenge. The crucial role played by diet and gut microbiota in brain development and functioning would indicate that modulating the gut-brain axis may help protect against the onset and progression of mental-health disorders. Some nutritional deficiencies and gut microbiota alterations have been linked to NDDs, suggesting their potential pathogenic implications. In addition, certain dietary interventions have emerged as promising alternatives or adjuvant strategies for improving the management of particular NDDs, at least in particular subsets of subjects. The gut microbiota can be a key to mediating the effects of other exposome factors such as diet on mental health, and ongoing research in Psychiatry and Neuropediatrics is developing Precision Nutrition Models to classify subjects according to a diet response prediction based on specific individual features, including microbiome signatures. Here, we review current scientific evidence for the impact of early life environmental factors, including diet, on gut microbiota and neuro-development, emphasizing the potential long-term consequences on health; and also summarize the state of the art regarding the mechanisms underlying diet and gut microbiota influence on the brain-gut axis. Furthermore, we describe the evidence supporting the key role played by gut microbiota, diet and nutrition in neurodevelopment, as well as the effectiveness of certain dietary and microbiome-based interventions aimed at preventing or treating NDDs. Finally, we emphasize the need for further research to gain greater insight into the complex interplay between diet, gut microbiome and brain development. Such knowledge would help towards achieving tailored integrative treatments, including personalized nutrition.
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The role of the microbiota-gut-brain axis in neuropsychiatric disorders.
Generoso, JS, Giridharan, VV, Lee, J, Macedo, D, Barichello, T
Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 2021;43(3):293-305
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Metabolites produced by the gut microbiota have been shown to influence mood and behaviour via the microbiota-gut-brain axis, and there is increased interest in better understanding this interaction in the context of mental health. This review summarises the evidence around the influence of gut microbiota in various neuropsychiatric disorders, primarily focusing on the metabolic pathways that originate in the gut microbiota. Current research highlights an association between gut microbiota metabolites with neuropsychiatric disorders and that probiotics demonstrate a significant therapeutic role in many of these disorders. Based on the current literature, the authors conclude it is crucial to better understand the complex microbiota-host interaction in health and disease, leading to more targeted and improved therapeutic interventions.
Abstract
The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.
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Probiotics, Prebiotics and Postbiotics on Mitigation of Depression Symptoms: Modulation of the Brain-Gut-Microbiome Axis.
Chudzik, A, Orzyłowska, A, Rola, R, Stanisz, GJ
Biomolecules. 2021;11(7)
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The bidirectional communication pathway between the gut microbiota and the central nervous system has been termed the brain-gut-microbiome axis. Increased investigation of this pathway has found the gut bacteria to impact metabolism and the brain, suggesting that modulating the microbiome may elicit change in mental health. The aim of this review is to discuss the current findings in both animal and human studies regarding the use of pro-, pre- and post-biotics in the prevention and treatment of depressive disorders. Studies show that modulating the bacteria in the gut may reduce inflammation, decrease stress hormone levels and adjust the levels of neurotransmitters in the brain. These changes consequently lead to the reduction of depressive symptoms and improvement in mood. While these results are promising, larger clinical trials are needed that include biochemical measurements and fecal microbiome analysis in addition to validated questionnaires. With this in mind, the authors conclude there is huge potential in the role of nutrition as a therapeutic target for neurological and mental health conditions.
Abstract
The brain-gut-microbiome axis is a bidirectional communication pathway between the gut microbiota and the central nervous system. The growing interest in the gut microbiota and mechanisms of its interaction with the brain has contributed to the considerable attention given to the potential use of probiotics, prebiotics and postbiotics in the prevention and treatment of depressive disorders. This review discusses the up-to-date findings in preclinical and clinical trials regarding the use of pro-, pre- and postbiotics in depressive disorders. Studies in rodent models of depression show that some of them inhibit inflammation, decrease corticosterone level and change the level of neurometabolites, which consequently lead to mitigation of the symptoms of depression. Moreover, certain clinical studies have indicated improvement in mood as well as changes in biochemical parameters in patients suffering from depressive disorders.
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The Role of the Gut Microbiota in Dietary Interventions for Depression and Anxiety.
Bear, TLK, Dalziel, JE, Coad, J, Roy, NC, Butts, CA, Gopal, PK
Advances in nutrition (Bethesda, Md.). 2020;11(4):890-907
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A growing body of research suggests diet and mental health are closely connected through the microbiome-gut-brain axis (MGBA). This axis shows how the gut and brain are linked in a bidirectional relationship, and provides a model in which dietary interventions could help prevent, or be an alternative therapy, for depression and anxiety. While there is an increased understanding of the complex interplay between diet, gut microbiome and mental health, the literature has produced conflicting results. The aim of this review is to discuss possible reasons for the conflicting results on the link between diet and mental health and present the current findings. The authors explored the impact of various dietary components on the MGBA including macronutrient ratios, omega 3 fatty acids, prebiotic and probiotic foods, food additives, and whole diet approaches. The research shows mental health is likely to be influenced by the MGBA via changes in gut microbiota composition and function, but conflicting results and limited research elucidates the complexity in understand the extent of this bidirectional relationship. Based on the current findings, the authors suggest dietary patterns for positive mental health should be in support of a healthy gut microbiota. They conclude further research is needed into the mechanisms in which gut microbiota impacts mental health to pave the way for a holistic approach to preventing and treating anxiety and depression.
Abstract
There is emerging evidence that an unhealthy dietary pattern may increase the risk of developing depression or anxiety, whereas a healthy dietary pattern may decrease it. This nascent research suggests that dietary interventions could help prevent, or be an alternative or adjunct therapy for, depression and anxiety. The relation, however, is complex, affected by many confounding variables, and is also likely to be bidirectional, with dietary choices being affected by stress and depression. This complexity is reflected in the data, with sometimes conflicting results among studies. As the research evolves, all characteristics of the relation need to be considered to ensure that we obtain a full understanding, which can potentially be translated into clinical practice. A parallel and fast-growing body of research shows that the gut microbiota is linked with the brain in a bidirectional relation, commonly termed the microbiome-gut-brain axis. Preclinical evidence suggests that this axis plays a key role in the regulation of brain function and behavior. In this review we discuss possible reasons for the conflicting results in diet-mood research, and present examples of areas of the diet-mood relation in which the gut microbiota is likely to be involved, potentially explaining some of the conflicting results from diet and depression studies. We argue that because diet is one of the most significant factors that affects human gut microbiota structure and function, nutritional intervention studies need to consider the gut microbiota as an essential piece of the puzzle.
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Gut microbes in neurocognitive and mental health disorders.
Halverson, T, Alagiakrishnan, K
Annals of medicine. 2020;52(8):423-443
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Adequately and effectively treating and managing neurocognitive disorders remains a challenge. Increasing evidence suggests gut microbes may contribute to common mental health disorders through the microbiota-gut-brain axis, and better understanding this interaction could lead to improved clinical outcomes. The aim of this review is to discuss the impact of the gut microbiome on neurocognitive and mental health disorders and the mechanisms by which they act. This review reveals that the gut microbiome can influence brain and intestinal cells and that there is an association between gut dysbiosis with different mental health and neurocognitive disorders. Additionally, evidence shows the antimicrobial effect of current pharmaceutical treatments used in mental disorders may adversely affect the gut microbiome. Based on these findings, the authors conclude the gut microbiome is likely involved in the pathophysiology of neurocognitive and mental health conditions. Treatment strategies focusing on the gut microbiome may have a role in the treatment and management of mental health disorders, however further evidence is needed before applying these strategies in clinical practice.
Abstract
INTRODUCTION As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders. RESULTS This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation. CONCLUSIONS This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.
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The Role of Bacteria and Its Derived Metabolites in Chronic Pain and Depression: Recent Findings and Research Progress.
Li, S, Hua, D, Wang, Q, Yang, L, Wang, X, Luo, A, Yang, C
The international journal of neuropsychopharmacology. 2020;23(1):26-41
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Depression is closely associated with chronic pain yet the connection between these comorbidities is ambiguous. Recent studies have shown alterations in the gut microbiome may contribute to cognitive dysfunction via the microbiota-gut-brain axis. The aim of this systematic review is to summarize the existing evidence of the role of the gut microbiome in chronic pain and depression and explore potential mechanisms of gut dysbiosis in the development of these conditions. This review found metabolic products from the gut microbiota can mediate neuro-inflammation and neuro-immunity pathways in pain and depression, and that dysbiosis in the gut may contribute to the cause of chronic pain and depression. The authors conclude the metabolic products from the gut bacteria offer new insights to the connection between the gut microbiota and mechanisms of pain and depression, while showing potential as a therapeutic target.
Abstract
BACKGROUND Chronic pain is frequently comorbid with depression in clinical practice. Recently, alterations in gut microbiota and metabolites derived therefrom have been found to potentially contribute to abnormal behaviors and cognitive dysfunction via the "microbiota-gut-brain" axis. METHODS PubMed was searched and we selected relevant studies before October 1, 2019. The search keyword string included "pain OR chronic pain" AND "gut microbiota OR metabolites"; "depression OR depressive disorder" AND "gut microbiota OR metabolites". We also searched the reference lists of key articles manually. RESULTS This review systematically summarized the recent evidence of gut microbiota and metabolites in chronic pain and depression in animal and human studies. The results showed the pathogenesis and therapeutics of chronic pain and depression might be partially due to gut microbiota dysbiosis. Importantly, bacteria-derived metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and secondary bile acids, offer new insights into the potential linkage between key triggers in gut microbiota and potential mechanisms of depression. CONCLUSION Studying gut microbiota and its metabolites has contributed to the understanding of comorbidity of chronic pain and depression. Consequently, modulating dietary structures or supplementation of specific bacteria may be an available strategy for treating chronic pain and depression.
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Gut hormones in microbiota-gut-brain cross-talk.
Sun, LJ, Li, JN, Nie, YZ
Chinese medical journal. 2020;133(7):826-833
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The bidirectional communication between the gastrointestinal tract and the brain, termed the gut-brain axis (GBA), is evidenced to to play a role in physiological and psychological health. While precise communication pathways are not yet clear, it is hypothesised this pathway may be an important therapeutic target in complex psychiatric and gastrointestinal disorders. The aim of this review is to summarize the role of gut hormones in the GBA and focus on how the microbiota interact with these hormones in health and disease. The literature shows the gut microbiota can affect the metabolism of various gut hormones, and these hormones can influence the microbiota. Evidence suggests this cross-talk may be a key regulator in appetite, immune response, stress response, and metabolism. Based on this review, the authors conclude the gut microbiota-hormone homeostatic relationship provides insight on the complex communication between the gut and the brain. They suggest future research should target the microbiota-hormones-gut-brain axis to develop new therapeutic strategies to psychiatric disorders.
Abstract
The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological health. The gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain axis. The interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain cross-talk. The microbiota plays an essential role in modulating many gut-brain axis-related diseases, ranging from gastrointestinal disorders to psychiatric diseases. Similarly, gut hormones also play pleiotropic and important roles in maintaining health, and are key signals involved in gut-brain axis. More importantly, gut microbiota can affect the release and functions of gut hormones. This review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological functions. Future studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders, such as obesity, anxiety, and depression.
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Nutrition Interventions in Rheumatoid Arthritis: The Potential Use of Plant-Based Diets. A Review.
Alwarith, J, Kahleova, H, Rembert, E, Yonas, W, Dort, S, Calcagno, M, Burgess, N, Crosby, L, Barnard, ND
Frontiers in nutrition. 2019;6:141
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Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by joint pain and inflammation with both genetic and modifiable risk factors. Research suggests a plant-based diet may play a role in management and remission. The aim of this review was to summarize the associations between plant-based diet patterns and RA symptoms. Current studies indicate an association between improvements in RA symptoms with weight loss and with plant-based diets. Based on these findings, the authors conclude excess weight and diets that include animal products may exacerbate symptoms associated with RA, whereas plant-based diets may help reduce pain and inflammation in these patients. The authors suggest further research is needed to test the effectiveness of plant-based diets on patients with RA.
Abstract
Rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease, affects roughly 1% of the world's population. RA pathogenesis remains unclear, but genetic factors account for 50-60% of the risk while the remainder might be linked to modifiable factors, such as infectious diseases, tobacco smoking, gut bacteria, and nutrition. Dietary triggers may play an inciting role in the autoimmune process, and a compromised intestinal barrier may allow food components or microorganisms to enter the blood stream, triggering inflammation. In addition, excessive body weight may affect pharmacotherapy response and the likelihood of disease remission, as well as the risk of disease mortality. Evidence suggests that changes in diet might play an important role in RA management and remission. Several studies have shown improvements in RA symptoms with diets excluding animal products. Studies have also shown that dietary fiber found in these plant-based foods can improve gut bacteria composition and increase bacterial diversity in RA patients, thus reducing their inflammation and joint pain. Although some of the trigger foods in RA patients are individualized, a vegan diet helps improve symptoms by eliminating many of these foods. This review examines the potential role of a plant-based diet in mediating RA symptoms. Further research is needed to test the effectiveness of plant-based diets on joint pain, inflammation, and quality of life in patients with RA.
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The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level.
Barton, W, Penney, NC, Cronin, O, Garcia-Perez, I, Molloy, MG, Holmes, E, Shanahan, F, Cotter, PD, O'Sullivan, O
Gut. 2018;67(4):625-633
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The human gut microbiome is known to actively influence metabolism, immunity and development. It has been shown that increased physical activity and healthy diet is associated with positive changes in faecal microbial diversity and composition compared with sedentary individuals. The aim of this study was to assess the metabolic activity of the microbiota between extremely active and sedentary individuals. Metabolic and genetic factors of the gut microbiome were analysed in 40 professional rugby players and 46 sedentary controls. This study found significant differences in faecal microbiota between athletes and sedentary controls at the functional metabolic level, providing deeper insight into the link between sustained physical activity and metabolic health. Based on these results, the authors conclude exercise may be an effective way to manipulate the gut microbiome and suggest further controlled trials be done to better understand the relationship between diet, exercise and the gut microbiome.
Abstract
OBJECTIVE It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.
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Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease.
Imhann, F, Vich Vila, A, Bonder, MJ, Fu, J, Gevers, D, Visschedijk, MC, Spekhorst, LM, Alberts, R, Franke, L, van Dullemen, HM, et al
Gut. 2018;67(1):108-119
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Patients with inflammatory bowel disease (IBD) present with a variety of clinical characteristics, making prevention, diagnosis and therapy very complex. Based on recent studies, it is hypothesised that the heterogeneity among patients with IBD is likely due to individual differences in the interaction between the host genome and gut microbiota. The aim of this case-control study was to analyse the gut microbiota, host genetics and clinical characteristics of 313 patients with IBD compared with 582 healthy controls. This extensive analysis has identified the gut microbiota as the key mediator in the development of IBD through new associations at the genetic and clinical level. Based on these findings, the authors conclude that a better understanding of gene-microbiota interactions can lead to new therapeutics and improved prevention strategies.
Abstract
OBJECTIVE Patients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case-control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD. DESIGN Stool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2. RESULTS Strikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10-13). CONCLUSIONS We show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.