A systematic review of microbiome changes and impact of probiotic supplementation in children and adolescents with neuropsychiatric disorders.

OBJECTIVES: In recent decades, the diagnostic and therapeutic implications of the microbiome changes and the impact of probiotic supplementation have increased rapidly. However, the potential for clinical translation of microbiome research for children and adolescents with psychiatric disorders is unclear. This review examined available evidence related to gut microbiota as well as the impact of probiotic supplementation on psychiatric disorders in the pediatric population reported to date. METHODS: We performed a literature search for the gut microbiota in child and adolescent population (0-18 years old) with mental health disorders from July 1999 through July 2019 in several databases: ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science. RESULTS: A total of 7 studies met inclusion criteria consisting of randomized controlled trials and cohort studies that examined various associations between psychiatric disorders and gut microbiota in youth. Six studies examined the effects of various treatment interventions such as probiotic supplementation on microbiota composition and behaviors. One study showed an increase in prosocial behavior in children with Autism Spectrum Disorder (ASD) and an increase in the Lachnospiraceae family following prebiotic supplementation. Another study suggested that prebiotic supplementation increased bifidobacterial populations for ASD and healthy controls. A study evaluating infant supplementation of prebiotics showed both a decreased likelihood of developing Attention Deficit Hyperactivity Disorder (ADHD) or ASD and decreased gut Bifidobacterium. One study did not find significant differences in microbiome composition after micronutrient treatment. CONCLUSION: The main goal of this systematic review was to comprehensively examine and summarize the current evidence focused on the potential effect of the relationship between microbiota gut composition as well as the effects of probiotic supplementation on psychiatric disorders in children and adolescents. This is a relatively new area of research and the number of included studies is limited. More studies are needed to determine whether gut dysbiosis leads to the development and/or contributes to the severity of mental disorders or whether gut dysbiosis is a result of other processes that accompany mental disorders. CLINICAL SIGNIFICANCE: A better understanding of the specific bacteria contributions, gut-brain pathways, and role in pathophysiological mechanisms in neuropsychiatric disorders in the child and adolescent populations can possibly provide alternative tools for a clinical psychiatrist. Moreover, it may ultimately aid the clinician with intervention strategies, or detect populations at risk for developing neuropsychiatric disorders.

Microbiota-gut-brain axis in health and disease: Is NLRP3 inflammasome at the crossroads of microbiota-gut-brain communications?

Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiology of major neurological and psychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). In particular, changes in gut microbiota can promote enteric and peripheral neurogenic/inflammatory responses, which, in turn, could contribute to neuroinflammation and neurodegeneration in the central nervous system (CNS). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiology and shaping the peripheral and central immune/inflammatory responses in CNS diseases. In this context, there is pioneering evidence supporting the existence of a microbiota-gut-inflammasome-brain axis, in which enteric bacteria modulate, via NLRP3 signaling, inflammatory pathways that, in turn, contribute to influence brain homeostasis. The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathology has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiology of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiology of CNS diseases, even though each disorder displays a different clinical picture.

Finding intestinal fortitude: Integrating the microbiome into a holistic view of depression mechanisms, treatment, and resilience.

Depression affects at least 322 million people globally, or approximately 4.4% of the world's population. While the earnestness of researchers and clinicians to understand and treat depression is not waning, the number of individuals suffering from depression continues to increase over and above the rate of global population growth. There is a sincere need for a paradigm shift. Research in the past decade is beginning to take a more holistic approach to understanding depression etiology and treatment, integrating multiple body systems into whole-body conceptualizations of this mental health affliction. Evidence supports the hypothesis that the gut microbiome, or the collective trillions of microbes inhabiting the gastrointestinal tract, is an important factor determining both the risk of development of depression and persistence of depressive symptoms. This review discusses recent advances in both rodent and human research that explore bidirectional communication between the gut microbiome and the immune, endocrine, and central nervous systems implicated in the etiology and pathophysiology of depression. Through interactions with circulating inflammatory markers and hormones, afferent and efferent neural systems, and other, more niche, pathways, the gut microbiome can affect behavior to facilitate the development of depression, exacerbate current symptoms, or contribute to treatment and resilience. While the challenge of depression may be the direst mental health crisis of our age, new discoveries in the gut microbiome, when integrated into a holistic perspective, hold great promise for the future of positive mental health.

The role of the brain-gut-microbiota axis in psychology: The importance of considering gut microbiota in the development, perpetuation, and treatment of psychological disorders.

INTRODUCTION: The prevalence of psychological disorders remains stable despite steady increases in pharmacological treatments suggesting the need for auxiliary treatment options. Consideration of the brain-gut-microbiota axis (BGMA) has made inroads into reconceptualizing psychological illness from a more holistic perspective. While our understanding of the precise role of gut microbiota (GM) in psychological illness is in its infancy, it represents an attractive target for novel interventions. METHOD: An extensive review of relevant literature was undertaken. RESULTS: Gut microbiota are proposed to directly and indirectly influence mood, cognition, and behavior which are key components of mental health. This paper outlines how GM may be implicated in psychological disorders from etiology through to treatment and prevention using the Four P model of case formulation. CONCLUSION: Moving forward, integration of GM into the conceptualization and treatment of psychological illness will require the discipline of psychology to undergo a significant paradigm shift. While the importance of the GM in psychological well-being must be respected, it is not proposed to be a panacea, but instead, an additional arm to a multidisciplinary approach to treatment and prevention.

The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.

Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.

Fevered Decisions: Race, Ethics, and Clinical Vulnerability in the Malarial Treatment of Neurosyphilis, 1922-1953.

Physicians deliberately inoculated marginalized patients with malaria, using them as reservoirs to facilitate malarial fever therapy for syphilitic patients. The history presents ethical questions in an evolving historical context.

The "psychomicrobiotic": Targeting microbiota in major psychiatric disorders: A systematic review.

The gut microbiota is increasingly considered as a symbiotic partner in the maintenance of good health. Metagenomic approaches could help to discover how the complex gut microbial ecosystem participates in the control of the host's brain development and function, and could be relevant for future therapeutic developments, such as probiotics, prebiotics and nutritional approaches for psychiatric disorders. Previous reviews focused on the effects of microbiota on the central nervous system in in vitro and animal studies. The aim of the present review is to synthetize the current data on the association between microbiota dysbiosis and onset and/or maintenance of major psychiatric disorders, and to explore potential therapeutic opportunities targeting microbiota dysbiosis in psychiatric patients.