THE MICROBIOTA IN GASTROINTESTINAL PATHOPHYSIOLOGY. IMPLICATIONS FOR HUMAN HEALTH, PREBIOTICS, PROBIOTICS, AND DYSBIOSIS

a Dedication
b Contributors
c About the Editors
d Introduction
e Part A: The Microbiota of the Gastrointestinal Tract
Chapter 1: The Upper Gastrointestinal Tract-Esophagus and Stomach
• Abstract
• Introduction
• The human microbiome projects
• Methods for microbial analysis and advances in sequencing technology
• Advances in microbiome research in the proximal versus distal gut
• The esophageal microbiome
• The microbiome in esophageal diseases
• Helicobacter pylori infection and its effect on the esophagus
• The gastric microbiome
• Impact of Helicobacter pylori infection on the composition of gastric microbiota
• Cofactors in the development of Helicobacter pylori-associated gastric adenocarcinoma
• Therapeutic interventions and their effect on the gastric physiology and microbiome
• Conclusions and perspectives
• Acknowledgments
Chapter 2: Characterizing and Functionally Defining the Gut Microbiota: Methodology and Implications
• Abstract
• Introduction
• Microbial niches of the intestines
• The 16S rRNA gene
• The human microbiota in health and disease
• Metagenomics of the human microbiome
• Transcriptomics and proteomics of the human microbiome
• 16S rRNA gene sequencing data analysis
• Defining microbiota function through gnotobiotics
• Integrating metaomic approaches to assess the efficacy of prebiotic and probiotic interventions
• Conclusions
Chapter 3: Microbiota of the Gastrointestinal Tract in Infancy
• Abstract
• Human microbiota
• Conclusions
• COI statement
• Acknowledgments
Chapter 4: Identification of the Microbiota in the Aging Process
• Abstract
• Introduction
• Gut microbiota, the hidden and forgotten organ
• Age-related gastroenterological changes
• Gut microbiota in the elderly
• Discrepancies in elderly microbiota
• Inflamm-aging
• Factors influencing changes in GM in the elderly
• Special problems of the older adult probably related to GM
• Inflammatory bowel disease
• Cancers
• Alzheimer’s disease
• Autoimmune diseases
• IBS and gut microbiota
• Drug metabolism
• Probiotics and prebiotics
• Summary, conclusions, projections for the future
f Part B: Common Organisms and Probiotics
Chapter 5: Escherichia coli Nissle 1917
• Abstract
• Introduction-history
• Fitness factors and probiotic mechanisms
• Clinical indications and applications (Table 5.2)
• Conclusions
Chapter 6: Probiotics of the Acidophilus Group: Lactobacillus acidophilus, delbrueckii subsp. bulgaricus and johnsonii
• Abstract
• Introduction
• Lactobacillus acidophilus
• Clinical trials of immunomodulation
• Clinical trials in digestive diseases
• Control of infectious disease
• Use in necrotizing enterocolitis
• Use in gynecological disorders
• Use in hepatic and metabolic disorders
• Lactobacillus bulgaricus
• Lactobacillus johnsonii
• Summary
Chapter 7: Lactobacillus rhamnosus GG
• Abstract
• History
• Bacteriology
• Antimicrobial susceptibility
• Molecular basis of LGG-host interactions
• Gene expression pattern in small bowel
• Potential safety concerns
• Clinical uses of LGG
• Summary
Chapter 8: Lactobacillus reuteri
• Abstract
• History
• Lactobacillus reuteri strains used in human trials, animal models, and in vitro studies
• Phylogeny and ecology of Lactobacillus reuteri
• Probiotic properties and mechanisms of action
• Use of Lactobacillus reuteri as a probiotic for the prevention and treatment of human disease
• Future directions and applications for Lactobacillus reuteri
• Acknowledgments
Chapter 9: The Use of Lactobacillus casei and Lactobacillus paracasei in Clinical Trials for the Improvement of Human Health
• Abstract
• Introduction
• Clinical trials employing L. casei and L. paracasei to treat digestives diseases
• Control of bacterial infections
• The effects of probiotics on immunity
• Probiotics in the enhancement of lipid metabolism
• Probiotics and cancer prevention
• Interventions for depressive disorders
• Conclusions
Chapter 10: Beneficial Influences of Lactobacillus plantarum on Human Health and Disease
• Abstract
• Introduction
• Trials that report the safety of Lactobacillus plantarum as a probiotic
• Lactobacillus plantarum-related trials for irritable bowel syndrome
• Metaanalysis of clinical trials
• Cardiovascular diseases, pancreatic diseases, and respiratory tract infections
• Gynecological and iron absorption influences
• Lactobacillus plantarum-induced influences on inflammation
• Lactobacillus plantarum-induced influences on metabolism
• Lactobacillus plantarum-induced influences on dermatological health
• Conclusions
Chapter 11: Use of Bacillus in Human Intestinal Probiotic Applications
• Abstract
• Introduction
• Use of Bacillus in food
• Advantages of forming endospores
• The rise in respectability of Bacillus probiotics
• Transient or inhabitant?
• Can an endospore former be metabolically active and be an effective probiotic?
• Therapeutic outcomes associated with Bacillus probiotics
• Future intestinal uses
Chapter 12: Bifidobacteria as Probiotic Organisms: An Introduction
• Abstract
Chapter 13: Bifidobacterium animalis spp. lactis
• Abstract
• Human studies
Chapter 14: Bifidobacterium bifidum
• Abstract
• Characterization and laboratory studies
• Clinical studies
• Safety
Chapter 15: Bifidobacterium breve
• Abstract
• Characterization and laboratory studies
• Clinical studies
• Safety
Chapter 16: Bifidobacterium longum
• Abstract
• Characterization and laboratory studies
• Clinical studies
• Safety
Chapter 17: Bifidobacterium longum spp. infantis
• Abstract
• Immunological and physiological effects
• Human studies
• Conclusions
Chapter 18: Common Organisms and Probiotics: Saccharomyces boulardii
• Abstract
• Introduction
• History
• Taxonomy
• Mechanisms of action
• Pharmacokinetics
• Clinical efficacy of Saccharomyces boulardii
• Treatment of acute pediatric diarrhea
• Antibiotic-associated diarrhea
• Helicobacter pylori infections
• Other diseases
• Inflammatory bowel disease
• Irritable bowel syndrome
• Acute adult diarrheas
• Traveler’s diarrhea
• Enteral nutrition-related diarrhea
• Necrotizing enterocolitis
• Clostridium difficile infections
• Giardiasis
• Human immunodeficiency virus diarrhea
• Sepsis
• Acne
• Hepatic function
• Safety of Saccharomyces boulardii
• Conclusions
• Acknowledgments
Chapter 19: Common Organisms and Probiotics: Streptococcus thermophilus (Streptococcus salivarius subsp. thermophilus)
• Abstract
• Introduction
• Taxonomy
• The shaping of a species by life in milk
• The ancestors of Streptococcus thermophilus
• Probiotic benefits
• The promise of in vitro and animal studies
Chapter 20: Complexities and Pitfalls in the Production of Multispecies Probiotics: The Paradigmatic Case of VSL#3 Formulation and Visbiome
• Abstract
• Claims for probiotics are product specific
• Composition of probiotic products and characterization of their beneficial effects are crucial
• Biosimilars-how similar is similar?
• Manufacturing changes can alter product characteristics
• The lately marketed product versus the original DS formulation of VSL#3-a comparison of selected parameters
• Conclusions
Chapter 21: The Viruses of the Gut Microbiota
• Abstract
• The eukaryotic virome, a component of the gut microbiome
• Interplay between gut virome and immune system
• Pathogenic viruses of the gut virome: enteropathogenic viruses associated with systemic infections
• Gut as a major source of neurotropic viruses, when pathogenesis and shedding is favored by humoral immune deficiency
• An uncertain status for diet-derived animal viruses
g Part C: Food Substrates Important to the Microbiota
Chapter 22: Dietary Fiber, Soluble and Insoluble, Carbohydrates, Fructose, and Lipids
• Abstract
• Introduction
• High fiber plant-based diets and chronic disease risk
• Dietary fiber and undigested carbohydrates
• Dietary fiber and carbohydrate fermentation
• Gut microbiota and diet link
• Plant-based diets and gut microbiota
• Gut microbiota and diet-related chronic diseases
• Antibiotics, blood lipids, and gut microbiota
• Fructose and the gut
• Hyposucrasia
• Conclusions
• Funding statement
• Competing interests
Chapter 23: Prebiotics: Inulin and Other Oligosaccharides
• Abstract
• Introduction
• Definitions
• Measurements
• Types
• Candidate Prebiotics
• Conclusions
Chapter 24: The Benefits of Yogurt, Cultures, and Fermentation
• Abstract
• General considerations about yogurt, fermented dairy products, and probiotics
• Benefits of yogurt and fermented dairy products
• Yogurt and nutrient density
• Yogurt and a balanced diet
• Yogurt and lactose intolerance
• Yogurt and weight management
• Yogurt, diabetes, and metabolic health
• Yogurt, heart health, blood pressure, and hypertension
• Yogurt and immune function
• Yogurt and digestive function
• Acknowledgments
• Disclaimer
h Part D: Basic Physiologic Effects of Microbiota
Chapter 25: Dysbiosis
• Abstract
• Introduction
• Dysbiosis
• Causes of dysbiosis (Table 25.2)
• Perinatal causes of dysbiosis
• How do we approach dysbiosis in the context of disease?
• Summary and conclusions
Chapter 26: Immunologic Response in the Host
• Abstract
• Intestinal epithelial cells
• Toll-like receptors and intestinal epithelial cells
• NOD receptors and intestinal epithelial cells
• Immunoregulatory role of intestinal epithelial cells
• Transcytosis of immunoglobulin A by intestinal epithelial cells
• Antigen presentation in the gut
• Role of dendritic cells
• Innate lymphoid cells
• T cells
• Microbial modulation of immune function
• Conclusions
Chapter 27: Gastrointestinal Microbiota and the Neural System
• Abstract
• Intestinal microbiota
• Microbiota and the brain
• Enteric nervous system
• Microbiota and the ENS
Chapter 28: Effect on the Host Metabolism
• Abstract
• Introduction
• Gut microbiota functions in host integrity
• Gut microbiota dysbiosis impact on host metabolism
• Conclusions
Chapter 29: Relationship Between Gut Microbiota, Energy Metabolism, and Obesity
• Abstract
• Introduction
• The gut microbiota extracts energy from the diet
• Regulation of fat storage through production of short-chain fatty acids
• Bacterial translocation contributes to obesity and associated disorders through low-grade inflammation
• The ANGPTL4 and AMPK pathways are involved in fat storage in germ-free mice
• The gut microbiota presents an important hope for future treatment options in obesity
Chapter 30: Taxonomic and Metagenomic Alterations of Microbiota in Bariatric Surgery
• Abstract
• Introduction
• Technology
• Obesity and microbiota
• Studies on bariatric surgery and the microbiome
Chapter 31: The Influence of Microbiota on Mechanisms of Bariatric Surgery
• Abstract
• The anatomic and physiologic changes that occur after bariatric surgery and how they alter the gut microbiome
• Energy harvest and FXR signaling hypotheses
• Lessons learned from bariatric surgery to create nonsurgical weight loss and metabolic treatments
i Part E: Management of Disease and Disorders by Prebiotics and Probiotic Therapy
Chapter 32: Allergic and Immunologic Disorders
• Abstract
• Introduction
• Gut microbiota
• Microbiota modulation strategies
• Clinical efficacy of probiotics/prebiotics
• Prevention of allergic diseases
• Treatment of allergic diseases
• Synbiotics
• Type 1 diabetes
• Celiac disease
• Conclusions
Chapter 33: Probiotics Use in Infectious Disease (Respiratory, Diarrhea, and Antibiotic-Associated Diarrhea)
• Abstract
• Introduction
• Acute respiratory infections
• Mechanisms of action
• Clinical impact
• Acute infectious diarrhea
• Antibiotic-associated and Clostridium difficile-associated diarrhea
• Necrotizing enterocolitis
• Conclusions
• Abbreviations
Chapter 34: FMT in Clostridium difficile and Other Potential Uses
• Abstract
• Introduction
• Fecal microbiota transplantation
• Donor selection and testing
• Preparation of fecal material and delivery
• Efficacy of FMT
• Mechanism of FMT
• Safety of FMT
• FMT for other conditions
• Conclusions
Chapter 35: Probiotics in the Treatment of Pouchitis
• Abstract
• Introduction
• Probiotics in pouchitis
• Conclusions
Chapter 36: Probiotic Treatment in Crohn’s Disease
• Abstract
• Introduction
• Rationale for using probiotics in Crohn’s disease
• Probiotic agents in the treatment of Crohn’s disease
• Conclusions
Chapter 37: Treatment of Inflammatory Bowel Disease in Ulcerative Colitis
• Abstract
• Introduction
• Probiotics
• Active ulcerative colitis
• Maintenance of ulcerative colitis
• Conclusions
Chapter 38: Treatment of Functional Bowel Disorders With Prebiotics and Probiotics
• Abstract
• Functional bowel disorders-definitions, epidemiology, and clinical conditions
• Conclusions and clinical implications of current data
• Abbreviations
Chapter 39: Celiac Disease, the Microbiome, and Probiotics
• Abstract
• Introduction
• Microbiota and celiac disease
• Gluten-free diet and microbiome
• CD genetics and microbiome
• Prebiotics and CD
• Probiotics and CD
• Conclusions
Chapter 40: Probiotics for the Treatment of Liver Disease
• Abstract
• Dysbiosis and liver disease
• Probiotics and liver disease
• Cirrhosis
• Conclusion and probiotics in clinical practice
Chapter 41: The Prevention and Treatment of Radiation and Chemotherapy-Induced Intestinal Mucositis
• Abstract
• Mucositis pathophysiology and the clinical problem
• Rationale for using probiotics
• Probiotics and intestinal cytoprotection in humans
• Limitations of available clinical data and proposals for future studies
• Prebiotics and the prevention of GI toxicity in radiotherapy
• Chemotherapy and gut microbiota
• Influence on probiotics on cancer therapeutics
• Summary
Chapter 42: The Role of the Brain-Gut-Microbiome in Mental Health and Mental Disorders
• Abstract
• Components of the brain-gut axis
• Examples of microbiome actions on the superorganism
• Examples of human brain effects on the microbiome
• Role of the gut-brain axis in specific disease states
• Mood disorders
• Autism
• Schizophrenia
• The behavioral effects of toxoplasmosis
Chapter 43: Management of Disease and Disorders by Prebiotics and Probiotic Therapy: Probiotics in Bacterial Vaginosis
• Abstract
• Introduction
• Bacterial vaginosis
• Rationale for using probiotics in bacterial vaginosis
• Clinical trials on probiotics use in bacterial vaginosis
• Formulations of probiotic bacteria for the treatment of bacterial vaginosis
• Conclusions
j Index

Features:
• Explains how to modify the gut microbiota and how the current strategies used to do this produce their effects
• Explores the gut microbiota as a therapeutic target
• Provides the synthesis of existing data from both mainstream and non-mainstream sources through experienced researchers in the field
• Serves as a ‘one-stop’ shop for a topic that’s currently spread across a number of various journals

Authors
• Martin H. Floch, MD, Clinical Professor of Medicine, Section of Gastroenterology and Nutrition, Yale University School of Medicine, Norwalk Hospital, Norwalk, CT.
• Yehuda Ringel, M.D. , Professor of Medicine, University of North Carolina, Chapel Hill, North Carolina.
• W. Allen Walker, M.D., Professor, Harvard School of Public Health, Boston, MA