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1.
Nutrition, Microbiota and Role of Gut-Brain Axis in Subjects with Phenylketonuria (PKU): A Review.
Verduci, E, Carbone, MT, Borghi, E, Ottaviano, E, Burlina, A, Biasucci, G
Nutrients. 2020;(11)
Abstract
The composition and functioning of the gut microbiota, the complex population of microorganisms residing in the intestine, is strongly affected by endogenous and exogenous factors, among which diet is key. Important perturbations of the microbiota have been observed to contribute to disease risk, as in the case of neurological disorders, inflammatory bowel disease, obesity, diabetes, cardiovascular disease, among others. Although mechanisms are not fully clarified, nutrients interacting with the microbiota are thought to affect host metabolism, immune response or disrupt the protective functions of the intestinal barrier. Similarly, key intermediaries, whose presence may be strongly influenced by dietary habits, sustain the communication along the gut-brain-axis, influencing brain functions in the same way as the brain influences gut activity. Due to the role of diet in the modulation of the microbiota, its composition is of high interest in inherited errors of metabolism (IEMs) and may reveal an appealing therapeutic target. In IEMs, for example in phenylketonuria (PKU), since part of the therapeutic intervention is based on chronic or life-long tailored dietetic regimens, important variations of the microbial diversity or relative abundance have been observed. A holistic approach, including a healthy composition of the microbiota, is recommended to modulate host metabolism and affected neurological functions.
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Histidine Metabolism and Function.
Brosnan, ME, Brosnan, JT
The Journal of nutrition. 2020;(Suppl 1):2570S-2575S
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Abstract
Histidine is a dietary essential amino acid because it cannot be synthesized in humans. The WHO/FAO requirement for adults for histidine is 10 mg · kg body weight-1 · d-1. Histidine is required for synthesis of proteins. It plays particularly important roles in the active site of enzymes, such as serine proteases (e.g., trypsin) where it is a member of the catalytic triad. Excess histidine may be converted to trans-urocanate by histidine ammonia lyase (histidase) in liver and skin. UV light in skin converts the trans form to cis-urocanate which plays an important protective role in skin. Liver is capable of complete catabolism of histidine by a pathway which requires folic acid for the last step, in which glutamate formiminotransferase converts the intermediate N-formiminoglutamate to glutamate, 5,10 methenyl-tetrahydrofolate, and ammonia. Inborn errors have been recognized in all of the catabolic enzymes of histidine. Histidine is required as a precursor of carnosine in human muscle and parts of the brain where carnosine appears to play an important role as a buffer and antioxidant. It is synthesized in the tissue by carnosine synthase from histidine and β-alanine, at the expense of ATP hydrolysis. Histidine can be decarboxylated to histamine by histidine decarboxylase. This reaction occurs in the enterochromaffin-like cells of the stomach, in the mast cells of the immune system, and in various regions of the brain where histamine may serve as a neurotransmitter.
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Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration.
Gentile, F, Doneddu, PE, Riva, N, Nobile-Orazio, E, Quattrini, A
International journal of molecular sciences. 2020;(20)
Abstract
Increasing evidence gives support for the idea that extra-neuronal factors may affect brain physiology and its predisposition to neurodegenerative diseases. Epidemiological and experimental studies show that nutrition and metabolic disorders such as obesity and type 2 diabetes increase the risk of Alzheimer's and Parkinson's diseases after midlife, while the relationship with amyotrophic lateral sclerosis is uncertain, but suggests a protective effect of features of metabolic syndrome. The microbiota has recently emerged as a novel factor engaging strong interactions with neurons and glia, deeply affecting their function and behavior in these diseases. In particular, recent evidence suggested that gut microbes are involved in the seeding of prion-like proteins and their spreading to the central nervous system. Here, we present a comprehensive review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function. Advancing technologies may allow researchers in the future to improve investigations in these fields, allowing the buildup of population-based preventive interventions and development of targeted therapeutics to halt progressive neurologic disability.
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Brain-gut-microbiome interactions in obesity and food addiction.
Gupta, A, Osadchiy, V, Mayer, EA
Nature reviews. Gastroenterology & hepatology. 2020;(11):655-672
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Abstract
Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain-gut-microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.
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Brain-heart interaction after acute ischemic stroke.
Battaglini, D, Robba, C, Lopes da Silva, A, Dos Santos Samary, C, Leme Silva, P, Dal Pizzol, F, Pelosi, P, Rocco, PRM
Critical care (London, England). 2020;(1):163
Abstract
Early detection of cardiovascular dysfunctions directly caused by acute ischemic stroke (AIS) has become paramount. Researchers now generally agree on the existence of a bidirectional interaction between the brain and the heart. In support of this theory, AIS patients are extremely vulnerable to severe cardiac complications. Sympathetic hyperactivity, hypothalamic-pituitary-adrenal axis, the immune and inflammatory responses, and gut dysbiosis have been identified as the main pathological mechanisms involved in brain-heart axis dysregulation after AIS. Moreover, evidence has confirmed that the main causes of mortality after AIS include heart attack, congestive heart failure, hemodynamic instability, left ventricular systolic dysfunction, diastolic dysfunction, arrhythmias, electrocardiographic anomalies, and cardiac arrest, all of which are more or less associated with poor outcomes and death. Therefore, intensive care unit admission with continuous hemodynamic monitoring has been proposed as the standard of care for AIS patients at high risk for developing cardiovascular complications. Recent trials have also investigated possible therapies to prevent secondary cardiovascular accidents after AIS. Labetalol, nicardipine, and nitroprusside have been recommended for the control of hypertension during AIS, while beta blockers have been suggested both for preventing chronic remodeling and for treating arrhythmias. Additionally, electrolytic imbalances should be considered, and abnormal rhythms must be treated. Nevertheless, therapeutic targets remain challenging, and further investigations might be essential to complete this complex multi-disciplinary puzzle. This review aims to highlight the pathophysiological mechanisms implicated in the interaction between the brain and the heart and their clinical consequences in AIS patients, as well as to provide specific recommendations for cardiovascular management after AIS.
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Irritable bowel syndrome.
Ford, AC, Sperber, AD, Corsetti, M, Camilleri, M
Lancet (London, England). 2020;(10263):1675-1688
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Abstract
Irritable bowel syndrome is a functional gastrointestinal disorder with symptoms including abdominal pain associated with a change in stool form or frequency. The condition affects between 5% and 10% of otherwise healthy individuals at any one point in time and, in most people, runs a relapsing and remitting course. The best described risk factor is acute enteric infection, but irritable bowel syndrome is also more common in people with psychological comorbidity and in young adult women than in the rest of the general population. The pathophysiology of irritable bowel syndrome is incompletely understood, but it is well established that there is disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and altered CNS processing. Other less reproducible mechanisms might include genetic associations, alterations in gastrointestinal microbiota, and disturbances in mucosal and immune function. In most people, diagnosis can be made on the basis of clinical history with limited and judicious use of investigations, unless alarm symptoms such as weight loss or rectal bleeding are present, or there is a family history of inflammatory bowel disease or coeliac disease. Once the diagnosis is made, an empathetic approach is key and can improve quality of life and symptoms, and reduce health-care expenditure. The mainstays of treatment include patient education about the condition, dietary changes, soluble fibre, and antispasmodic drugs. Other treatments tend to be reserved for people with severe symptoms and include central neuromodulators, intestinal secretagogues, drugs acting on opioid or 5-HT receptors, or minimally absorbed antibiotics (all of which are selected according to predominant bowel habit), as well as psychological therapies. Increased understanding of the pathophysiology of irritable bowel syndrome in the past 10 years has led to a healthy pipeline of novel drugs in development.
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Adolescence and Aging: Impact of Adolescence Inflammatory Stress and Microbiota Alterations on Brain Development, Aging, and Neurodegeneration.
Yahfoufi, N, Matar, C, Ismail, N
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(7):1251-1257
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Abstract
Puberty/adolescence is a critical phase during neurodevelopment with numerous structural, neurochemical, and molecular changes occurring in response to genetic and environmental signals. A consequence of this major neuronal reorganizing and remodeling is a heightened level of vulnerability to stressors and immune challenges. The gut microbiota is a fundamental modulator of stress and immune responses and has been found to play a role in mental health conditions and neurodegenerative disorders. Environmental insults (stress, infection, neuroinflammation, and use of antibiotics) during adolescence can result in dysbiosis subsidizing the development of brain disorders later in life. Also, pubertal neuroinflammatory insults can alter neurodevelopment, impact brain functioning in an enduring manner, and contribute to neurological disorders related to brain aging, such as Alzheimer's disease, Parkinson's disease, and depression. Exposure to probiotics during puberty can mitigate inflammation, reverse dysbiosis, and decrease vulnerabilities to brain disorders later in life. The goal of this review is to reveal the consequences of pubertal exposure to stress and immune challenges on the gut microbiota, immune reactivity within the brain, and the risk or resilience to stress-induced mental illnesses and neurodegenerative disorders. We propose that the consumption of probiotics during adolescence contribute to the prevention of brain pathologies in adulthood.
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Diabesity and mood disorders: Multiple links through the microbiota-gut-brain axis.
Farzi, A, Hassan, AM, Zenz, G, Holzer, P
Molecular aspects of medicine. 2019;:80-93
Abstract
The global prevalence of diabesity is on the rise, and the clinical, social and economic health burden arising from this epidemic is aggravated by a significant co-morbidity of diabesity with neuropsychiatric disease, particularly depression. Importantly, not only is the prevalence of mood disorders elevated in patients with type 2 diabetes, depressed patients are also more prone to develop diabetes. This reciprocal relationship calls for a molecular and systemic analysis of diabesity-brain interactions to guide preventive and therapeutic strategies. The analysis we are presenting in this review is modelled on the microbiota-gut-brain axis, which provides the brain with information from the gut not only via the nervous system, but also via a continuous stream of microbial, endocrine, metabolic and immune messages. This communication network offers important clues as to how obesity and diabetes could target the brain to provoke neuropsychiatric disease. There is emerging evidence that the gut microbiota is orchestrating a multiplicity of bodily functions that are intimately related to the immune, metabolic and nervous systems and that gut dysbiosis spoils the homeostasis between these systems. In our article we highlight two groups of molecular links that seem to have a significant bearing on the impact of diabesity on the brain. On the one hand, we focus on microbiota-related metabolites such as short-chain fatty acids, tryptophan metabolites, immune stimulants and endocannabinoids that are likely to play a mediator role. On the other hand, we discuss signalling molecules that operate primarily in the brain, specifically neuropeptide Y, brain-derived neurotrophic factor and γ-amino butyric acid, that are disturbed by microbial factors, obesity and diabetes and are relevant to mental illness. Finally, we address the usefulness of diet-related interventions to suspend the deleterious relationship between diabesity and mood disorders.
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[The microbiota-gut-brain axis and its great projections].
Gomez-Eguilaz, M, Ramon-Trapero, JL, Perez-Martinez, L, Blanco, JR
Revista de neurologia. 2019;(3):111-117
Abstract
INTRODUCTION The microbiota is the set of millions of microorganisms that coexist in a symbiotic way in our body. It is mainly located in the digestive tract, being distributed in function of the chemical properties and the functions of the different organs. The factors that influence its composition are multiple (diet, individual habits, diseases or drugs). It also participates in several functions of the organism such as metabolism, immunity or even the function of the central nervous system. DEVELOPMENT This last interrelationship is called: gut-brain axis. For years the relationship between the microbiota and the central nervous system has been known and how they influence one over the other. It is postulated that communication occurs through three systems: the vagus nerve, the systemic pathway (with the release of hormones, metabolites and neurotransmitters) and the immune system (by the action of cytokines). CONCLUSIONS There are still many unknowns to be clarified in this field, but this microbiota-intestine-brain relationship is postulated as a possible pathogenic basis for neurological diseases of great health impact such as Alzheimer, Parkinson or multiple sclerosis. There are currently studies with probiotics with hopeful results in patients with Alzheimer's disease.
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10.
Inflammatory Bowel Disease: A Stressed "Gut/Feeling".
Oligschlaeger, Y, Yadati, T, Houben, T, Condello Oliván, CM, Shiri-Sverdlov, R
Cells. 2019;(7)
Abstract
Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory condition, hallmarked by a disturbance in the bidirectional interaction between gut and brain. In general, the gut/brain axis involves direct and/or indirect communication via the central and enteric nervous system, host innate immune system, and particularly the gut microbiota. This complex interaction implies that IBD is a complex multifactorial disease. There is increasing evidence that stress adversely affects the gut/microbiota/brain axis by altering intestinal mucosa permeability and cytokine secretion, thereby influencing the relapse risk and disease severity of IBD. Given the recurrent nature, therapeutic strategies particularly aim at achieving and maintaining remission of the disease. Alternatively, these strategies focus on preventing permanent bowel damage and concomitant long-term complications. In this review, we discuss the gut/microbiota/brain interplay with respect to chronic inflammation of the gastrointestinal tract and particularly shed light on the role of stress. Hence, we evaluated the therapeutic impact of stress management in IBD.