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The gut microbiome and pharmacology: a prescription for therapeutic targeting of the gut-brain axis.
New frontiers for host-microbe interactions continue to emerge as our knowledge of the adult gut microbiome in health and disease is continually supplemented and improved. Alterations in the gut microbiota composition in irritable bowel syndrome (IBS) are now linked to symptom severity while population-based evidence linking gut microbiome signatures to depression is an important new landmark. The effects of drugs on gut microbiome composition are also becoming clearer. Meanwhile, preclinical studies have delineated the influence of the gut microbiome at a structural and activity level in distinct brain regions. Bacterial metabolites, such as tryptamine, can activate specific receptors to impact gastrointestinal motility. These recent studies bring into focus the future implications for therapeutic targeting of the microbiome-gut-brain axis.
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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) has been implicated in disorders of brain-gut interaction, including irritable bowel syndrome, and in neuropsychiatric disorders, including depression, Alzheimer's disease, and autism spectrum disorder. Further, alterations in the gut microbiome have been implicated in the pathogenesis of organic gastrointestinal diseases, including inflammatory bowel disease. The BGMA is an attractive therapeutic target, as using prebiotics, probiotics, or postbiotics to modify the gut microbiome or mimic gut microbial signals could provide novel treatment options to address these debilitating diseases. However, despite significant advancements in our understanding of the BGMA, clinical data is lacking. In this article, we will review current understanding of the comorbidity of gastrointestinal diseases and psychological disorders. We will also review the current evidence supporting the key role of the BGMA in this pathology. Finally, we will discuss the clinical implications of the BGMA in the evaluation and management of psychological and gastrointestinal disorders.
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Microbiota abnormalities and the therapeutic potential of probiotics in the treatment of mood disorders.
Major depressive disorder (MDD) and bipolar disorder (BD) are among the leading causes of burden and disability worldwide. Despite intensified research efforts to improve the treatment options and remission rates in mood disorders, no disease modifying treatment exists for these disorders. Accumulating evidence implicates the involvement of the gut microbiota in processes relevant to etiopathology of central nervous system-based disorders. The objective of this article was to critically evaluate the evidence supporting the link between gastrointestinal microbiota and mood disorders and to discuss the potential benefits of using probiotics in the treatment of MDD and BD. The concept of psychobiotics, which is bacterial-based interventions with mental health benefit, is emerging in the field. On the other hand, while probiotics might potentially represent a significant advance, specific roles of microbiota in the pathophysiology of mood disorders still need further investigation along with intervention studies.
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A Summary of the Fourth Annual Virology Education HIV Microbiome Workshop.
Each year, a growing international collection of researchers meets at the NIH to share and discuss developments in the microbiome HIV story. This past year has seen continued progress toward a detailed understanding of host-microbe interactions both within and outside the field of HIV. Commensal microbes are being linked to an ever-growing list of maladies and physiologic states, including major depressive disorder, chronic kidney disease, and Parkinson disease. PubMed citations for "microbiome" are growing at an exponential rate with over 11,000 in 2018. Various microbial taxa have been associated with HIV infection, and some of these taxa associated with HIV infection have also been associated with systemic markers of inflammation in HIV infected individuals. Causality remains unclear however as environmental and behavioral factors may drive HIV risk, inflammation, and gut enterotype. Much of the work currently being done addresses potential mechanisms by which gut microbes influence immune and inflammatory pathways. No portion of the microbiome landscape has grown as rapidly as study of the interplay between gut microbes and response to cancer immunotherapy. As Dr. Wargo discussed in her keynote address, this area has opened the door to better understanding on how commensal microbes interact with the human immune system.
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Assessing the relationship of gut microbiota with neurological, psychiatric, and neurodegenerative disorders: a narrative review.
OBJECTIVES: The gut-brain axis is a bidirectional communication network regulated by the immune, nervous, and endocrine systems, microbial metabolites, and environmental factors such as diet, stress, circadian rhythm, and drugs/chemicals. This review aims to examine current literature on the link between gut microbiota dysbiosis and major brain disorders, and to explore strategies for improving patient outcomes. METHODS: This narrative (non-systematic) review investigated the association between gut microbiota dysbiosis and psychiatric (schizophrenia, major depressive disorder, bipolar disorder, eating disorders), neurological (autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, migraine), and neurodegenerative disorders (Parkinson's disease, Alzheimer's disease, multiple sclerosis). It also considered potential microbiota- and neuroprotective interventions. RESULTS: The existing body of evidence consistently links gut dysbiosis with neuropsychiatric and neurodegenerative conditions through mechanisms including inflammation, impaired intestinal barriers, microbial production of neurotransmitters or toxins, and accumulation of α-synuclein or amyloid affecting neurogenesis and myelination. Balanced dietary patterns and the use of probiotics, prebiotics, or fermented foods are associated with healthier gut microbiota and improved neurological function. CONCLUSIONS: Further research is needed to clarify whether gut dysbiosis causes or contributes to these disorders, and to develop evidence-based, gut-focused practical recommendations for their prevention and management.
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Beyond metabolic messengers: Bile acids and TGR5 as pharmacotherapeutic intervention for psychiatric disorders.
Psychiatric disorders pose a significant global health challenge, exacerbated by the COVID-19 pandemic and insufficiently addressed by the current treatments. This review explores the emerging role of bile acids and the TGR5 receptor in the pathophysiology of psychiatric conditions, emphasizing their signaling within the gut-brain axis. We detail the synthesis and systemic functions of bile acids, their transformation by gut microbiota, and their impact across various neuropsychiatric disorders, including major depressive disorder, general anxiety disorder, schizophrenia, autism spectrum disorder, and bipolar disorder. The review highlights how dysbiosis and altered bile acid metabolism contribute to the development and exacerbation of these neuropsychiatric disorders through mechanisms involving inflammation, oxidative stress, and neurotransmitter dysregulation. Importantly, we detail both pharmacological and non-pharmacological interventions that modulate TGR5 signaling, offering potential breakthroughs in treatment strategies. These include dietary adjustments to enhance beneficial bile acids production and the use of specific TGR5 agonists that have shown promise in preclinical and clinical settings for their regulatory effects on critical pathways such as cAMP-PKA, NRF2-mediated antioxidant responses, and neuroinflammation. By integrating findings from the dynamics of gut microbiota, bile acids metabolism, and TGR5 receptor related signaling events, this review underscores cutting-edge therapeutic approaches poised to revolutionize the management and treatment of psychiatric disorders.
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Overview and systematic review of studies of microbiome in schizophrenia and bipolar disorder.
Schizophrenia and bipolar disorder are among the leading causes of disability, morbidity, and mortality worldwide. In addition to being serious mental illnesses, these disorders are associated with considerable systemic physiological dysfunction, including chronic inflammation and elevated oxidative stress. The advent of sophisticated sequencing techniques has led to a growing interest in the potential role of gut microbiota in human health and disease. Advances in this area have transformed our understanding of a number of medical conditions and have generated a new perspective suggesting that gut microbiota might be involved in the development and maintenance of brain/mental health. Animal models have demonstrated strong though indirect evidence for a contributory role of intestinal microbiota in psychiatric symptomatology and have linked the microbiome with neuropsychiatric conditions. We present a systematic review of clinical studies of microbiome in schizophrenia and bipolar disorder. The published literature has a number of limitations; however, the investigations suggest that these disorders are associated with reduced microbial diversity and show global community differences compared to non-psychiatric comparison samples. In some reports, specific microbial taxa were associated with clinical disease characteristics, including physical health, depressive and psychotic symptoms, and sleep, but little information on the functional potential of those community changes. Studies also suggest increased intestinal inflammation and permeability, which may be among the principal mechanisms by which microbial dysbiosis impacts systemic physiological functioning. We highlight gaps in the current literature and implications for diagnosis and therapeutic interventions, and outline future directions for microbiome research in psychiatry.
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The Impact of Probiotic Supplements on Cognitive Parameters in Euthymic Individuals with Bipolar Disorder: A Pilot Study.
INTRODUCTION: Cognitive dysfunction is prevalent in depressive as well as manic episodes in individuals with Bipolar Disorder (BD). Even more, after symptom remission, many individuals with BD experience persisting cognitive impairment also in euthymic periods, leading to high illness burden and low quality of life. According to a recent research in animals and healthy humans, microbiota may influence cognitive processes via the brain-gut axis. A strategy to examine the role of the microbiota in different diseases is the intake of supplements that modulate the gut microbiome. The aim of this pilot study was to analyze the impact of probiotic supplements on cognitive parameters in a cohort of euthymic individuals with BD, receiving daily probiotic treatment over a time period of 3 months. METHODS: A total of 20 euthymic individuals with BD received probiotic supplement over a time period of 3 months and completed a cognitive test battery at 3 time points (t1 at time of inclusion, t2 after one month and t3 after 3 months of probiotic intake). RESULTS: We found a significant improvement of performance concerning attention and psychomotor processing speed measured with the Digit Symbol Test after one (t2) as well as after 3 months (t3) of treatment (F = 8.60; η2 = 0.49, p < 0.01). Furthermore, executive function measured with the TMT-B, increased significantly over 3 months (F = 3.68; η2 = 0.29, p < 0.05). CONCLUSION: The results confirm the hypotheses that probiotic supplement might help stable individuals with BD to improve the cognitive function, which in turn might lead to better psychosocial, occupational, work and financial functioning. Nevertheless, the idea of this potential new treatment is challenging because of the variety of the human's gut microbiota.
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The Brain-Gut-Microbiome Axis Across the Life Continuum and the Role of Microbes in Maintaining the Balance of Health.
There is a growing body of evidence that the interaction between various microbial organisms and the human host can affect various physical and even mental health conditions. Bidirectional communication occurs between the brain and the gut microbiome, referred to as the brain-gut-microbiome axis. During aging, changes occur to the gut microbiome due to various events and factors such as the mode of delivery at birth, exposure to medications (e.g., antibiotics), environmental exposures, diet, and host genetics. Connections to the brain-gut-microbiome axis through different systems also change during aging, leading to the development of chronic diseases. Disruption of the gut microbiome, known as dysbiosis, can lead to a reduction in beneficial bacteria and a corresponding increase in more harmful or even pathogenic bacteria. This imbalance may predispose or contribute to the development of various health conditions and illnesses. Targeted treatment of the gut microbiome and the brain-gut-microbiome axis may assist in the overall management of these various ailments. The purpose of this review is to describe the changes that occur in the gut microbiome throughout life, and to highlight the risk factors for microbial dysbiosis. We discuss the different health conditions experienced at various stages of life, and how dysbiosis may contribute to the clinical presentation of these diseases. Modulation of the gut microbiome and the brain-gut-microbiome axis may therefore be beneficial in the management of various ailments. This review also explores how various therapeutics may be used to target the gut microbiome. Gut biotics and microbial metabolites such as short chain fatty acids may serve as additional forms of treatment. Overall, the targeting of gut health may be an important strategy in the treatment of different medical conditions, with nutritional modulation of the brain-gut-microbiome axis also representing a novel strategy.
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"WHAT'S BUGGING THE GUT IN OCD?" A REVIEW OF THE GUT MICROBIOME IN OBSESSIVE-COMPULSIVE DISORDER.
The gut microbiome has become a topic of major interest as of late, with a new focus specifically on psychiatric disorders. Recent studies have revealed that variations in the composition of the gut microbiota may influence anxiety and mood and vice versa. Keeping the concept of this bidirectional "microbiota-gut-brain" axis in mind, this review aims to shed light on how these findings may also be implicated in obsessive-compulsive disorder (OCD); potentially outlining a novel etiological pathway of interest for future research in the field.