Gut microbiome and the brain

The Microbiome-Gut-Brain Axis in Health and Disease.: Gut microbes are capable of producing most neurotransmitters found in the human brain. Evidence is accumulating to support the view that gut microbes influence central neurochemistry and behavior. Irritable bowel syndrome is regarded as the prototypic disorder of the brain-gut-microbiota axis that can be responsive to probiotic therapy. Translational studies indicate that certain bacteria may have an impact on stress responses and cognitive functioning. Manipulating the gut microbiota with psych

The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options.: Parkinson's disease is a common neurodegenerative disorder in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alterations in the gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved

How Microbes Affect Depression: Underlying Mechanisms via the Gut-Brain Axis and the Modulating Role of Probiotics.: Accumulating evidence suggests that the gut microbiome influences the brain functions and psychological state of its host via the gut-brain axis, and gut dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown that a depletion of the gut microbiota leads to behavioral changes, and is associated with pathological changes, including abnormal stress response and impaired adult neurogenesis. Short-chain fatty acids such as butyr

The Microbiota-Gut-Brain Axis.: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age

Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis.: The high comorbidity of psychological disorders in both functional and organic gastrointestinal diseases suggests the intimate and complex link between the brain and the gut. Termed the brain-gut axis, this bidirectional communication between the central nervous system and enteric nervous system relies on immune, endocrine, neural, and metabolic pathways. There is increasing evidence that the gut microbiome is a key part of this system, and dysregulation of the brain-gut-microbiome axis (BGMA) h

Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder.: The prevalence of autism spectrum disorders (ASD) is increasing, but its etiology remains elusive and hence an effective treatment is not available. Previous research conducted on animal models suggests that microbiota-gut-brain axis may contribute to ASD pathology and more human research is needed. This study was divided into two stages,.At the discovery stage, we compared the differences in gut microbiota profiles (using 16S rRNA sequencing), fecal SCFAs (using GC-MS) and plasma neurotransmitt

Drosophila C virus systemic infection leads to intestinal obstruction.

Unlabelled: Drosophila C virus (DCV) is a positive-sense RNA virus belonging to the Dicistroviridae family. This natural pathogen of the model organism Drosophila melanogaster is commonly used to investigate antiviral host defense in flies, which involves both RNA interference and inducible responses. Although lethality is used routinely as a readout for the efficiency of the antiviral immune response in these studies, virus-induced pathologies in flies still are poorly understood. Here, we characterize the pathogenesis associated with systemic DCV infection. Comparison of the transcriptome of flies infected with DCV or two other positive-sense RNA viruses, Flock House virus and Sindbis virus, reveals that DCV infection, unlike those of the other two viruses, represses the expression of a large number of genes. Several of these genes are expressed specifically in the midgut and also are …

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The effects of acute tryptophan depletion on affective behaviour and cognition in Brown Norway and Sprague Dawley rats.

Previous studies in rats and humans have shown that the essential amino acid tryptophan (TRP) is depleted after consumption of a gelatin-based protein-carbohydrate mixture, which is lacking L-tryptophan (TRP-). In rats, TRP depletion caused impaired object recognition but only had a modest effect on affective behaviour. Because these studies were preformed with Wistar rats, the aim of the present experiment was to evaluate strain differences in behavioural responses to acute TRP depletion between Brown Norway (BN) and Sprague Dawley (SD) rats. The rats were repeatedly treated with TRP- or a balanced control (TRP+) and were tested in tests of anxiety- and depression-related behaviour (open-field test, home cage emergence test, social interaction test, forced swim test) and memory. SD rats, but not BNs, showed more anxiety- and depression-related behaviour and impaired object recognition a…

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The antibacterial properties of Malaysian tualang honey against wound and enteric microorganisms in comparison to manuka honey.

Background: Antibiotic resistance of bacteria is on the rise, thus the discovery of alternative therapeutic agents is urgently needed. Honey possesses therapeutic potential, including wound healing properties and antimicrobial activity. Although the antimicrobial activity of honey has been effectively established against an extensive spectrum of microorganisms, it differs depending on the type of honey. To date, no extensive studies of the antibacterial properties of tualang (Koompassia excelsa) honey on wound and enteric microorganisms have been conducted. The objectives of this study were to conduct such studies and to compare the antibacterial activity of tualang honey with that of manuka honey. Methods: Using a broth dilution method, the antibacterial activity of tualang honey against 13 wound and enteric microorganisms was determined; manuka honey was used as the control. Different …

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Negative mood affects brain processing of visceral sensation.

Background & aims: A link between negative emotional state and abnormal visceral sensation has been frequently reported. However, the influence of negative emotion on brain processing of painful visceral sensations has not been investigated. We used functional magnetic resonance imaging (fMRI) and negative emotional stimuli to investigate the effects of negative emotion on brain processing of esophageal sensation. Methods: Twelve healthy male volunteers (age range, 21-32 years) participated in the study. Negative emotion was induced using emotionally valent music. fMRI images were acquired during 2 experimental runs; throughout these, volunteers received randomized nonpainful and painful distentions to the esophagus during neutral and negative emotion. Subjective perception of each stimulus was acquired, as were mood ratings. Results: Sadness ratings increased significantly following neg…

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Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?

Background & aims: Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic-pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. Methods: A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Results: Cortisol and the proinflammatory cytokines interleukin (IL)-6 (toget…

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Fasting as a Multisystem Health Modulator: A Narrative Review of Metabolic, Cardiovascular, Immune, Neurocognitive, and Psychospiritual Effects.

Background: Fasting, practiced in clinical, cultural, and faith-based contexts, has emerged as a non-pharmacological strategy capable of modulating multiple physiological systems. Contemporary evidence suggests that diverse fasting patterns (intermittent and time-restricted fasting, Ramadan fasting, alternate-day and periodic fasting, dry fasting, and fasting-mimicking diets) converge on shared metabolic-circadian-immune pathways and can be conceptualized within an integrated resilience framework. Aim: This narrative review synthesizes current experimental and human data on fasting as a multisystem health modulator, linking metabolic, cardiovascular, immune, gut-liver-microbiome, neurocognitive, endocrine, and psychospiritual effects to common regulatory axes, particularly the Metabolic-Circadian-Immune (MCI) and Energy-Information-Resilience (EIR) models. Results: Across fasting modalit…

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The Therapeutic Role of Ketogenic Diet in Neurological Disorders.

The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the pote…

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Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders.

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 brain disorders. The BGM system is made up of neuroendocrine, neural, and immune communication channels which establish a network of bidirectional interactions between the brain, the gut and its microbiome. Diet not only plays a crucial role in shaping the gut microbiome, but it can modulate structure and function of the brain through these communication channels. In this review, we summarize the evidence available from preclinical and clinical studies on the influence of dietary habits and interventions on a selected group of psychiatric and neurologic disorders including depression, cognitive decline, Parkinson's disease, autism spectrum disorder and epilepsy. We will particularly address the role of diet-induced …

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Intermittent fasting contributes to aligned circadian rhythms through interactions with the gut microbiome.

The timing of food consumption is considered to be an important modulator of circadian rhythms, regulating a wide range of physiological processes which are vital to human health. The exact mechanisms underlying this relationship are not fully understood, but likely involve alterations in the structure and functioning of the gut microbiome. Therefore, this narrative review aims to clarify these mechanisms by focusing on intermittent fasting as a dietary strategy of food timing. A literature search identified 4 clinical and 18 preclinical studies that examined either (1) the impact of intermittent fasting on the gut microbiome, or (2) whether circadian rhythms of the host are subject to changes in the bacterial populations in the gut. Results reveal that intermittent fasting directly influences the gut microbiome by amplifying diurnal fluctuations in bacterial abundance and metabolic acti…

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An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease.

The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, life-style risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion…

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Diet, Stress and Mental Health.

Introduction: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established. Methods: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress. Results: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood …

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Diet, inflammation and the gut microbiome: Mechanisms for obesity-associated cognitive impairment.

Poor diet and obesity are associated with cognitive impairment throughout adulthood, and increased dementia risk in aging. Here we review the current literature interrogating the mechanisms by which diets high in fat, or fat and sugar lead to cognitive impairment, focusing on changes to gut microbiome composition, inflammatory signalling and blood-brain barrier integrity. Preclinical studies indicate weight gain is not necessary for diet-induced cognitive impairment. Rather, gut microbiome composition, and systemic and central inflammatory processes appear to contribute to diet-induced cognitive impairment. While both obese humans and rodents exhibit reduced blood-brain barrier integrity, cognitive impairments precede these changes, suggesting other mechanisms may underly diet-induced cognitive changes. Other potential candidates include hormone, glucoregulatory and cardiovascular change…

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Nutritional psychiatry: Towards improving mental health by what you eat.

Does it matter what we eat for our mental health? Accumulating data suggests that this may indeed be the case and that diet and nutrition are not only critical for human physiology and body composition, but also have significant effects on mood and mental wellbeing. While the determining factors of mental health are complex, increasing evidence indicates a strong association between a poor diet and the exacerbation of mood disorders, including anxiety and depression, as well as other neuropsychiatric conditions. There are common beliefs about the health effects of certain foods that are not supported by solid evidence and the scientific evidence demonstrating the unequivocal link between nutrition and mental health is only beginning to emerge. Current epidemiological data on nutrition and mental health do not provide information about causality or underlying mechanisms. Future studies sh…

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Diet and Inflammation in Cognitive Ageing and Alzheimer's Disease.

Purpose of review: Nutrition is known to modulate the immune system and may alter neuroinflammatory processes implicated in the pathogenesis of Alzheimer's disease (AD) and progression of neurodegeneration. Here, we review the evidence for healthy dietary patterns and age-related cognition and discuss potential neuroinflammatory actions of diet on cognitive function. Recent findings: Anti-inflammatory dietary patterns such as the Mediterranean diet (MD) and dietary approaches to stop hypertension (DASH) may be neuroprotective. Several dietary components consumed in the MD and DASH (omega-3 fatty acids, antioxidants and polyphenols) can inhibit neuroinflammation associated with AD. Anti-inflammatory diets may also attenuate neuroinflammation via indirect immune pathways from the gut microbiome and systemic circulation. Diet may influence cognitive ageing via several inflammatory pathways.…

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Bile Acids as Metabolic Regulators and Nutrient Sensors.

Bile acids facilitate nutrient absorption and are endogenous ligands for nuclear receptors that regulate lipid and energy metabolism. The brain-gut-liver axis plays an essential role in maintaining overall glucose, bile acid, and immune homeostasis. Fasting and feeding transitions alter nutrient content in the gut, which influences bile acid composition and pool size. In turn, bile acid signaling controls lipid and glucose use and protection against inflammation. Altered bile acid metabolism resulting from gene mutations, high-fat diets, alcohol, or circadian disruption can contribute to cholestatic and inflammatory diseases, diabetes, and obesity. Bile acids and their derivatives are valuable therapeutic agents for treating these inflammatory metabolic diseases.

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Allostatic load and ageing: linking the microbiome and nutrition with age-related health.

Ageing is a process of decline in physiological function and capability over time. It is an anticipated major burden on societal health-care costs due to an increasingly aged global population. Accelerated biological ageing is a feature of age-related morbidities, which also appear to share common underpinning features, including low-grade persistent inflammation, phosphate toxicity, diminished Nrf2 activity, a depleted metabolic capability, depressed mitochondrial biogenesis and a low diversity gut microbiome. Social, psychological, lifestyle and nutritional risk factors can all influence the trajectory of age-related health, as part of an individual's exposome, which reflects the interplay between the genome and the environment. This is manifest as allostatic (over)load reflecting the burden of lifestyle/disease at both a physiological and molecular level. In particular, age-related ge…

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NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings.

Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD). The Nod-like receptor pyrin containing 3 inflammasome (NLRP3) is an intracellular multiprotein complex responsible for a number of innate immune processes associated with infection, inflammation and autoimmunity. Recent data have demonstrated that NLRP3 activation appears to bridge the gap between imm…

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Metabolic Effects of Intermittent Fasting.

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved health outcomes. A MEDLINE search was performed using PubMed and the terms "intermittent fasting," "fasting," "time-restricted feeding," and "food timing." Modified fasting regimens appear to promote weight loss and may improve metabolic health. Several lines of evidence also support the hypothesis that eating patterns that reduce or eliminate nighttime eating and prolong nightly fasting intervals may result in sustained improvements in human health. Intermittent fasting regimens are hypothesized to influence metabolic regulation via effects on (a) circadian biology, (b) the gut microbiome, and (c) modifiable lifestyle behaviors, such as slee…

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Brain-Heart Interaction: Cardiac Complications After Stroke.

Neurocardiology is an emerging specialty that addresses the interaction between the brain and the heart, that is, the effects of cardiac injury on the brain and the effects of brain injury on the heart. This review article focuses on cardiac dysfunction in the setting of stroke such as ischemic stroke, brain hemorrhage, and subarachnoid hemorrhage. The majority of post-stroke deaths are attributed to neurological damage, and cardiovascular complications are the second leading cause of post-stroke mortality. Accumulating clinical and experimental evidence suggests a causal relationship between brain damage and heart dysfunction. Thus, it is important to determine whether cardiac dysfunction is triggered by stroke, is an unrelated complication, or is the underlying cause of stroke. Stroke-induced cardiac damage may lead to fatality or potentially lifelong cardiac problems (such as heart fa…

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The Central Nervous System and the Gut Microbiome.

Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain barrier, myelination, neurogenesis, and microglia maturation and also modulates many aspects of animal behavior. H…

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Paternal microbiome perturbations impact offspring fitness.

The gut microbiota operates at the interface of host-environment interactions to influence human homoeostasis and metabolic networks1-4. Environmental factors that unbalance gut microbial ecosystems can therefore shape physiological and disease-associated responses across somatic tissues5-9. However, the systemic impact of the gut microbiome on the germline-and consequently on the F1 offspring it gives rise to-is unexplored10. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable ant…

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Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome.

Background: Obstructive sleep apnea (OSA)-hypopnea syndrome (OSAHS) has been recognized as a comorbidity of type 2 diabetes mellitus (T2DM); more than half of T2DM patients suffer from OSAHS. Intermittent hypoxia (IH) plays an important role in metabolic diseases, such as obesity and OSAHS, through various mechanisms, including altering the gut microecological composition and function. Therefore, it is important to study the role of gut microbiota in T2DM patients with OSAHS, which has a high incidence and is prone to several complications. Aim: To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS. Methods: Seventy-eight participants were enrolled from Henan Province People's Hospital and divided into healthy control (HC, n = 26), T2DM (n = 25), and T2DM + OSA (n = 27) groups based on their conditions. The fecal bacterial DNA of the research parti…

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Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice.

Chemotherapy treatment is associated with acute behavioral side effects (fatigue, anorexia) that significantly reduce patient quality of life and are dose-limiting, thereby increasing mortality (Kidwell et al., 2014). Disruptions to gut homeostasis (diarrhea, constipation, microbial dysbiosis) are also observed in patients receiving chemotherapy. In non-oncological patients, facets of mental health (fatigue, anxiety, depression) correlate with alterations in the gut microbiome, suggestive of a contribution of the gut in CNS disease etiology. The potential gut-to-brain pathway is poorly understood in patients receiving chemotherapy. Our prior studies have demonstrated a correlation between chemotherapy treatment, gut changes, peripheral and central inflammation, and behavioral symptoms in mice. Here we aimed to determine the extent to which chemotherapy-associated gut manipulations modula…

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Effect of Clostridium butyricum against Microglia-Mediated Neuroinflammation in Alzheimer's Disease via Regulating Gut Microbiota and Metabolites Butyrate.

Scope: Recent evidences demonstrate that abnormal gut microbiota (GM) might be involved in the pathogenesis of Alzheimer's disease (AD). However, the role of probiotics in preventing AD by regulating GM-gut-brain axis remains unclear. Here, the anti-neuroinflammatory effect and its mechanism of probiotic Clostridium butyricum (CB) against AD is investigated by regulating GM-gut-brain axis. Methods and results: APPswe/PS1dE9 (APP/PS1) transgenic are treated intragastrically with CB for 4 weeks then cognitively tested. Amyloid-β (Aβ) burden, microglial activation, proinflammatory cytokines production, GM, and metabolites butyrate are analyzed. Moreover, Aβ-induced BV2 microglia are pretreated with butyrate, and the levels of cluster of differentiation 11b (CD11b), cyclooxygenase-2 (COX-2), and NF-κB p65 phosphorylation are determined. The results show that CB treatment prevents cognitive i…

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Intermittent Fasting Improves Lipid Metabolism Through Changes in Gut Microbiota in Diet-Induced Obese Mice.

BACKGROUND The mechanism of how intermittent fasting (IF) improves metabolism is not fully understood. Our study aimed to explore the effect of IF on lipid metabolism in obese mice, specifically on the intestinal flora. MATERIAL AND METHODS Diet-induced obese (DIO) mice were subjected to ad libitum (AL) feeding or IF (alternate-day fasting) for 30 days. We examined the lipid metabolism, fat distribution, gene expression of lipid metabolism, and intestinal flora in the mice. RESULTS Despite having access to the same high-fat diet as the AL-fed groups, IF mice displayed pronounced weight loss, and their lipid metabolism significantly improved, mainly reflected in lower serum lipid levels and ameliorated liver steatosis. IF also reduced metabolic endotoxemia in DIO mice. The 16S ribosomal deoxyribonucleic acid gene amplicon sequencing suggested that IF did not change the community richness …

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