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

The effects of probiotics on depressive symptoms in humans: a systematic review.

Background: Patients suffering from depression experience significant mood, anxiety, and cognitive symptoms. Currently, most antidepressants work by altering neurotransmitter activity in the brain to improve these symptoms. However, in the last decade, research has revealed an extensive bidirectional communication network between the gastrointestinal tract and the central nervous system, referred to as the "gut-brain axis." Advances in this field have linked psychiatric disorders to changes in the microbiome, making it a potential target for novel antidepressant treatments. The aim of this review is to analyze the current body of research assessing the effects of probiotics, on symptoms of depression in humans. Methods: A systematic search of five databases was performed and study selection was completed using the preferred reporting items for systematic reviews and meta-analyses process…

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Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice.

Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host, including amelioration of anxiety-like behavior and psychiatric illnesses. Here we administered Lactobacillus plantarum PS128 (PS128) to a germ-free (GF) mouse model to investigate the impact of the gut-brain axis on emotional behaviors. First, we demonstrated that chronic administration of live PS128 showed no adverse effects on physical health. Then, we found that administration of live PS128 significantly increased the total distance traveled in the open field test and decreased the time spent in the closed arm in the elevated plus maze test, whereas the administration of PS128 had no significant effects in the depression-like behaviors of GF mice. Also, chronic live PS128 ingestion significantly increased the levels of both serotonin and dopamine in the striatum, but not in th…

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Oral health's inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions.

The landscape in dentistry is changing as emerging studies continue to reveal that periodontal health impacts systemic health, and vice versa. Population studies, clinical studies, and in vitro animal studies underscore the critical importance of oral health to systemic health. These inextricable relationships come to the forefront as oral diseases, such as periodontal disease, take root. Special populations bring to bear the multimodal relationships between oral and systemic health. Specifically, periodontal disease has been associated with diabetes, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer. Although bidirectional relationships are recognized, the potential for multiple comorbidities, relationships, and connections (multimodal relationships) also exists. Proposed …

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Brain-Gut-Microbiota Axis in Alzheimer's Disease.

Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding…

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Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders.

Psychobiotics are a group of probiotics that affect the central nervous system (CNS) related functions and behaviors mediated by the gut-brain-axis (GBA) via immune, humoral, neural, and metabolic pathways to improve not only the gastrointestinal (GI) function but also the antidepressant and anxiolytic capacity. As a novel class of probiotics, the application of psychobiotics has led researchers to focus on a new area in neuroscience. In the past five years, some psychobiotics strains were reported to inhibit inflammation and decreased cortisol levels, resulting in an amelioration of the symptoms of anxiety and depression. Psychobiotics are efficacious in improving neurodegenerative and neurodevelopmental disorders, including autism spectrum disorder (ASD), Parkinson's disease (PD) and Alzheimer's disease (AD). Use of psychobiotics can improve GI function, ASD symptoms, motor functions o…

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Intermittent Fasting: Is the Wait Worth the Weight?

Purpose of review: We review the underlying mechanisms and potential benefits of intermittent fasting (IF) from animal models and recent clinical trials. Recent findings: Numerous variations of IF exist, and study protocols vary greatly in their interpretations of this weight loss trend. Most human IF studies result in minimal weight loss and marginal improvements in metabolic biomarkers, though outcomes vary. Some animal models have found that IF reduces oxidative stress, improves cognition, and delays aging. Additionally, IF has anti-inflammatory effects, promotes autophagy, and benefits the gut microbiome. The benefit-to-harm ratio varies by model, IF protocol, age at initiation, and duration. We provide an integrated perspective on potential benefits of IF as well as key areas for future investigation. In clinical trials, caloric restriction and IF result in similar degrees of weight…

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Deciphering the virus-to-prokaryote ratio (VPR): insights into virus-host relationships in a variety of ecosystems.

The discovery of the numerical importance of viruses in a variety of (aquatic) ecosystems has changed our perception of their importance in microbial processes. Bacteria and Archaea undoubtedly represent the most abundant cellular life forms on Earth and past estimates of viral numbers (represented mainly by viruses infecting prokaryotes) have indicated abundances at least one order of magnitude higher than that of their cellular hosts. Such dominance has been reflected most often by the virus-to-prokaryote ratio (VPR), proposed as a proxy for the relationship between viral and prokaryotic communities. VPR values have been discussed in the literature to express viral numerical dominance (or absence of it) over their cellular hosts, but the ecological meaning and interpretation of this ratio has remained somewhat nebulous or contradictory. We gathered data from 210 publications (and addit…

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The stomach-brain axis.

The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion o…

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Clinical studies of lactoferrin in children.

Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. The aim of this study was to review all clinical studies of lactoferrin (LF) in children in an effort to determine which interventions may improve pediatric care or require further research. We conducted a systematic and critical review of published literature and found 19 clinical studies that have used human or bovine LF for different outcomes: iron metabolisms and anemia (6 studies), fecal flora (5 studies), enteric infections (3 studies), common pediatric illnesses (1 study), immunomodulation (3 studies), and neonatal sepsis (1 study). Although the efficacies have varied in each trial, the main finding of all published studies is the safety of the intervention. Protection agains…

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Diagnosis and management of IBS.

IBS is a common gastrointestinal condition characterized by chronic or recurrent abdominal pain associated with altered bowel habits. IBS is considered a functional bowel disorder (that is, not defined by structural or biochemical abnormalities) and is diagnosed using symptom-based criteria. Limited and judicious use of diagnostic testing is recommended, particularly in patients with typical symptoms of IBS without alarm signs and symptoms. Management of IBS is based on a multifactorial approach and includes establishment of an effective patient-provider relationship, education, reassurance, dietary alterations, pharmacotherapy, behavioral and psychological treatment. Patient-centered care is recommended, in which management is focused on the patient's most bothersome and impactful symptoms, their preferences and previous experiences with treatment, and addressing factors associated with…

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Systemic amyloidosis and the gastrointestinal tract.

Systemic amyloidosis is characterized by the extracellular deposition of protein in an abnormal fibrillar form. Several different types of amyloidosis exist, each defined by the identity of their respective fibril precursor protein. Among patients with systemic amyloidosis, histological involvement of the gastrointestinal tract is very common but is often subclinical. Conversely, primary diseases of the gastrointestinal tract can cause systemic amyloidosis; for example, AA amyloidosis can occur secondary to IBD. The presence and pattern of gastrointestinal symptoms varies substantially, not only between the different types of amyloidosis but also within them. Typical clinical presentations, most of which are nonspecific, include macroglossia, hemorrhage, motility disorders, disturbance of bowel habit and malabsorption. Endoscopic and radiological features are also nonspecific, with the s…

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Pathophysiological mechanisms of stress-induced intestinal damage.

Stress has been shown to have both central and peripheral effects, promoting psychological illness (such as anxiety and depression), as well influencing peripheral disease in the intestine. Stress in humans can exacerbate symptoms of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), lowering visceral pain thresholds and decreasing mucosal barrier function. Studies in rodents have revealed that both acute and chronic exposure to stressors can lead to pathophysiology of the small and large intestine, including altered ion secretion and increased epithelial permeability (by both transcellular and paracellular pathways). Prolonged exposure to stress can induce low-grade inflammation, cause ultrastructural epithelial abnormalities, and alter bacterial-host interactions allowing greater microbial translocation. In this review, we discuss the stress response and the effects o…

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Infection-induced viscerosensory signals from the gut enhance anxiety: implications for psychoneuroimmunology.

Infection and inflammation lead to changes in mood and cognition. Although the "classic" sickness behavior syndrome, involving fatigue, social withdrawal, and loss of appetites are most familiar, other emotional responses accompany immune activation, including anxiety. Recent studies have shown that gastrointestinal bacterial infections lead to enhanced anxiety-like behavior in mice. The bacteria-induced signal is most likely carried by vagal sensory neurons, and occurs early on (within 6h) during the infection. These signals induce evidence of activation in brain regions that integrate viscerosensory information with mood, and potentiate activation in brain regions established as key players in fear and anxiety. The findings underline the importance of viscerosensory signals arising from the gastrointestinal tract in modulation of behaviors appropriate for coping with threats, and sugge…

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Brain-gut connections in functional GI disorders: anatomic and physiologic relationships.

Understanding the neural regulation of gut function and sensation makes it easier to understand the interrelatedness of emotionality, symptom-attentive behavior or hypervigilance, gut function and pain. The gut and the brain are highly integrated and communicate in a bidirectional fashion largely through the ANS and HPA axis. Within the CNS, the locus of gut control is chiefly within the limbic system, a region of the mammalian brain responsible for both the internal and external homeostasis of the organism. The limbic system also plays a central role in emotionality, which is a nonverbal system that facilitates survival and threat avoidance, social interaction and learning. The generation of emotion and associated physiologic changes are the work of the limbic system and, from a neuroanatomic perspective, the 'mind-body interaction' may largely arise in this region. Finally, the limbic …

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The microbiome-gut-brain axis: from bowel to behavior.

The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity…

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Functional gastrointestinal disorders: advances in understanding and management.

Gastrointestinal symptoms are highly prevalent, but many people who have them will have no organic explanation for their symptoms. Most of these people will be labelled as having a functional gastrointestinal disorder, such as irritable bowel syndrome, functional dyspepsia, or functional constipation. These conditions affect up to 40% of people at any one point in time, and two-thirds of these people will have chronic, fluctuating symptoms. The pathophysiology of functional gastrointestinal disorders is complex, but involves bidirectional dysregulation of gut-brain interaction (via the gut-brain axis), as well as microbial dysbiosis within the gut, altered mucosal immune function, visceral hypersensitivity, and abnormal gastrointestinal motility. Hence, nomenclature refers to the conditions as disorders of gut-brain interaction. Psychological comorbidity is common; however, whether or no…

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Correlation between human gut microbiome and diseases.

Human gut microbiome is a major source of human bacterial population and a significant contribution to both positive and harmful effects. Due to its involvement in a variety of interactions, gut microorganisms have a great impact on our health throughout our lives. The impact of gut microbial population is been studied intensively in last two decades. Extensive literature survey focusing developments in the field were searched in English language Electronic Databases like PubMed, Google Scholar, Pubag, Google books, and Research Gate were mostly used to understand the role of human gut mirobiome and its role in different human diseases. Gut microbiome in healthy subjects differs from those who suffer from diseases. Type 2 diabetes, obesity, non-alcoholic liver disease, and cardiometabolic diseases have all been linked to dysbiosis of the gut microbiota. Pathogenesis of many disorders is …

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Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota.

The development of colonic diverticulosis is a common aging change in industrialized nations. While most patients have asymptomatic diverticulosis, around one in five develops symptomatic diverticular disease. This is characterized by recurrent abdominal pain and disturbed bowel habit. Some of the pain episodes are prolonged and are due to acute diverticulitis, which itself may be complicated by abscess, perforation, fistulation, or stricture formation. Risk factors favouring the development of symptomatic diverticular disease include obesity, smoking and diets low in fiber but high in red meat and animal fat. What determines the transition from asymptomatic diverticulosis to symptomatic diverticular disease is unclear but neuromuscular changes following acute diverticulitis may be responsible in some cases. The severity of symptoms generated depends on cerebral pain processing which is …

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Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry.

The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability, nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledge of the human microbiome increases, including its connection to mental health (for example, anxiety and depression), it is becoming increasingly clear that there are untold connections between our resident microbes and many aspects of physiology. Of relevance to this research are new findings concerning the ways in which fermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals (for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids) may act…

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Alcoholic liver disease: pathogenesis, management, and novel targets for therapy.

Alcohol use is a leading cause of preventable morbidity and mortality worldwide, with much of its negative impact as the result of alcoholic liver disease (ALD). ALD is a broad term that encompasses a spectrum of phenotypes ranging from simple steatosis to steatohepatitis, progressive fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the development of these different disease stages are incompletely understood. Standard treatment of ALD, which includes abstinence, nutritional support, and corticosteroids, has not changed in the last 40 years despite continued poor outcomes. Novel therapies are therefore urgently needed. The development of such therapies has been hindered by inadequate resources for research and unsuitable animal models. However, recent developments in translational research have allowed for identification of new potential targets for therapy. T…

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Enteroendocrine cell signalling via the vagus nerve.

Nutrient delivery to the gut activates neuroendocrine mechanisms that control digestion and energy intake and utilisation. These include the release from enteroendocrine cells of mediators including 5HT, CCK, GLP-1, PYY and ghrelin that act on vagal afferent neurons regulating food intake and autonomic reflexes controlling motility, secretion, inflammatory responses and mucosal defence. The mediators may act locally on vagal afferent fibres running close to their cell of origin, or distally after delivery in the circulation. Recent work indicates that the signalling mechanisms are strongly influenced by nutrient status. Thus, both food withdrawal and diet-induced obesity alter the sensitivity of vagal afferent neurons to stimulation as well as their patterns of expression of receptors and neuropeptide transmitters. Normally, leptin potentiates vagal afferent stimulation by CCK but this i…

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Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour.

Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS--possibly through neural, endocrine and immune pathways--and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorder…

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Maternal separation as a model of brain-gut axis dysfunction.

Rationale: Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS. Object…

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Review article: the psychoneuroimmunology of irritable bowel syndrome--an exploration of interactions between psychological, neurological and immunological observations.

Background: The pathogenesis of irritable bowel syndrome (IBS) is founded on interactive mechanisms. Disentangling these processes is a prerequisite for the development of effective drug therapy. Aim: To identify the interaction between the various factors implicated in IBS. Methods: Articles pertaining to IBS pathogenesis focusing on psychoneuroimmunology were identified using following search terms: IBS, animal models, microbiota, probiotics, immunology, visceral hypersensitivity, imaging, psychology and visceral pain. Results: Cerebral imaging using MRI and proton emission tomography scanning has revealed differential regional cerebral activation, whereas stimuli induced activation has been captured by both MRI and cortical evoked potentials. At the peripheral neurological level, the concept of visceral hypersensitivity has been challenged as perhaps representing psychological traits …

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The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature.

Introduction: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutritio…

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