The Microbiome and the Brain

Description

Brain related disorders are among the most challenging health issues of our time. The development of effective therapeutic and preventive strategies for these disorders relies on a comprehensive understanding of the underlying causative mechanisms. And, until recently, these mechanisms have remained somewhat elusive. The newly discovered pivotal role of the intestinal microbiome in brain health, functionality, and resistance to disease is revolutionizing neuroscience. The Microbiome and the Brain, through the contributions of some of the most forward thinking researchers and clinicians in the field, comprehensively reveals the leading edge of our understanding of the fundamental role of gut microbes and their metabolites in a wide array of seemingly diverse brain issues including Alzheimer’s disease, autism, multiple sclerosis, and mood disorders. In addition, mechanisms defining these relationships are explored along with a presentation of the state-of-the-art as it relates to interpretation of relevant laboratory assessments. Finally, novel therapeutic opportunities, derived from this exciting science are presented. Readers will learn: The highly validated relationship between alterations of gut microbes and their metabolites, and risk for Alzheimer’s disease. The important link between autism and intestinal dysbiosis. Appropriate interpretation of available laboratory assessments of the intestinal microbiome. The potential role of fecal microbial transplant in neurological diseases. The influence of diet and other lifestyle choices on the microbiome as it relates to brain health and functionality. Cover Half Title Title Page Copyright Page Contents Editor List of Contributors Introduction Chapter 1: Assessing the Microbiome—Current and Future Technologies and Applications Methods for Sequencing the Microbiome 16S rRNA Sequencing Shotgun Metagenomic Sequencing Generating Data from Samples Common Descriptive Analysis Techniques for Microbiome Data Diversity Analysis Relative Abundance Plots Functional Genomics Critical Appraisal of Microbiome Data Simple, Community-Level Analyses—16S rRNA Sequencing Detailed Metagenomic Analyses—Shotgun Metagenomic Sequencing References Chapter 2: The Microbiome – Role in Personalized Medicine Introduction The Microbiome and Its Impact on Cellular Modulation The Uniqueness of the Microbiome-Brain Connection Influence of the Microbiome on Immunometabolism Taking it Personally: Dynamic Human Exposure and the Microbiome Precision Personalized Medicine from the Microbiome Notes Chapter 3: Immune Response to Microbial Toxins in Inflammatory and Neurodegenerative Disorders Introduction The Role of Bacterial Toxins in Inflammatory and Autoimmune Disorders Bacterial Toxins Breaking the Gut and Blood–Brain Barriers The Role of LPS in the Breakdown of the Blood–Brain Barrier and the Induction of Pathology in the CNS Correlation of Intestinal Bacterial LPS Antibody with Occludin/Zonulin, S100B and Aquaporin 4 Association of Gram-Negative Bacterial Molecules (LPS, BCdT) with Alzheimer’s Disease (AD) Circulating Antibodies against Bacterial Toxins May Become Pathogenic in the Context of BBB Breakdown Conclusion References Chapter 4: The Microbiome—Its Role in Neuroinflammation: The Autism Spectrum Disorder Paradigm Cross Communication between Brain and Gastrointestinal System: The Gut–Brain Axis Combined Gut and Blood–Brain Barriers Defects ASD as a Prototypical Example of Gut–Brain Axis Dysfunction CONCLUSION References Chapter 5: Nutrition and the Microbiome—Implications for Autism Spectrum Disorder Introduction ASD and Microbiota ASD and Microbial Metabolites Gastrointestinal Symptoms and ASD Nutritional Challenges in Children with ASD Influence of Diet on Microbiota Composition Interventions Targeting the Microbiota in ASD to Manage Symptoms Potential Role of Nutrition in the Microbiota-to-Brain Communication in ASD Conclusions and Future Directions References Chapter 6: Alzheimer’s Disease, the Microbiome, and 21st Century Medicine Looking Forward References Chapter 7: Microbial Involvement in Alzheimer’s Disease Introduction: AD and Human Microbiome Gut Microbiota and Alzheimer’s Impaired Microbiota and Alzheimer’s Human microbiome and risk factors of AD Targeting Gut Microbiota for AD Interventions Future Directions Conclusions References Chapter 8: The Role of the Microbiome in Mood INTRODUCTION The Gut and its Microbiota Brain-Gut Microbiota Axis Brain-Gut Microbiota Signaling Pathways and Molecules Signaling Pathways Molecules Influence of Environmental Factors on the Brain-Gut Microbiota Axis in Health Infections and Antibiotics Prebiotics and Probiotics Diet and Exercise Early Life Adversity and Stress Sex Differences The Role of Gut Microbiota Related to Anxiety and Depression Depression Anxiety BGMA-based Treatment in Mood Disorders: Beyond Probiotics Conclusions References Chapter 9: The Microbiome in Multiple Sclerosis\ Introduction The Epidemiology and Importance of MS The MS Disease Courses and Trajectories Summary Comments on Major Unmet Needs in MS The Microbiome and Multiple Sclerosis: Evidence from Animal Models Circumstantial or Indirect Evidence Suggesting a Role of the Gut Microbiome in Multiple Sclerosis Does the Gut Microbiota Differ between Individuals with Multiple Sclerosis and Controls? Comment on Study Design Summary Remarks What Are They Doing? Exploring the Functional Capacity of the Gut Microbiome Is the gut microbiota associated with subsequent multiple sclerosis activity? Beyond the Gut Bacteria Manipulating the Multiple Sclerosis Microbiome What’s Next for Multiple Sclerosis and the Gut Microbiome? References Chapter 10: Bacteriophage Involvement in Neurodegenerative Diseases Introduction Bacteriophages and Neurodegeneration Bacteriophages, Eukaryotic Cells, and Autoimmunity Bacteriophages and Protein Misfolding Neurodegeneration and Phage-Induced Microbiota Disease Bacteriophages and Pathogen-Associated Molecular Pattern (PAMPs) Conclusions Acknowledgments References Chapter 11: The Role of Fecal Microbiota Transplantation in Neurological Diseases Introduction Enteric Virome Gut Mycobiome Archaea Gut Bacteria How Do Bacteria Influence Human Behavior? Microvesicles Neuronal Interaction Fecal Microbiota Transplantation Issues Experimental Clinical Use of Fecal Microbiota Transplantation in Neurological Disorders The Gut Effects of Fecal Microbiota Transplantation on Hepatic Encephalopathy Effects of Fecal Microbiota Transplantation on Epilepsy Conclusions Notes Bibliography Chapter 12: Lifestyle Influences on the Microbiome Introduction Dietary Patterns and the Gut Microbiome Gut Microbial Food Networks Human Paradoxes Dietary Alteration of Gut Microbial Metabolism D-Lactic Acidosis Hyperammonemia Gut Fermentation: Fructose, Fructans, and Irritable Bowel Syndrome Minor Dietary Components and the Gut Microbiome Effects of Exercise on the Gut Microbiome How Stress and Inflammation Impact the Gut Microbiome Substance Use and the Microbiome Alcohol Tobacco Medications Conclusion Notes Index