Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications

Front Cover Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications Copyright Contents Contributors Introduction to the Microbiome and Metabolome HISTORY SCIENTIFIC APPROACHES THE BIRTH OF CURRENT MICROBIOME STUDIES THE METABOLOME AND OTHER THE ERA OF MULTIOMICS REFERENCES Useful Internet Sites I - Tools, Toolstations and Models 1 - Germ-Free Animals as a Tool to Study Indigenous Microbiota INTRODUCTION OBTAINING AND MAINTAINING GERM-FREE ANIMALS Purpose of Use Germ-Free Animals Gnotobiotic Animals Gnotobiotic Animals With Simplified Microbial Consortia Germ-Free Animals With Transplanted Eubiotic or Dysbiotic Microbiota From the Same or Other Animal Species Conventionalized or Conventional Animals CONCLUSION REFERENCES 2 - Germ-Free Mouse Technology in Cardiovascular Research THE VARIOUS WAYS TO STUDY HOST-MICROBIAL INTERACTIONS A Short History of Germ-Free Research Some Thoughts and Concerns on the Present Status of Germ-Free Research THE COMMENSAL IMPACT ON THE MATURATION AND VIGILANCE OF IMMUNITY Adaption of Lymphoid Tissues Keeping Commensals at Bay Alterations of Immune Cell Function GNOTOBIOTIC COLONIZATION AND METAORGANISMAL PATHWAYS DEFINED FLORA AND IMMUNE STIMULATION REGULATORY T CELLS T HELPER CELLS TH1 AND TH17 REGIII-γ PEPTIDE INTESTINAL ANGIOGENESIS IMPACT OF THE COMMENSAL MICROBIOTA ON VASCULAR FUNCTION Vascular Remodeling Brain Capillary Network Vascular Dysfunction and Hypertension THE EMERGING LINK BETWEEN MICROBIOTA AND CARDIOVASCULAR DISEASE Influence of Innate Immune Signaling on Atherosclerosis Antiatherogenic Bacteria TLR2 Signaling, Myeloid Cells, and Atherosclerosis Influence of the Microbiota Versus Germ-free or Antibiotic Treatment Microbiota-Derived Metabolite Trimethylamine-N-Oxide Trimethylamine-N-Oxide and Human Disease Implications of the Microbiota in Thrombosis Endothelial Platelet Deposition Vascular Events in Inflammatory Bowel Disease PERSPECTIVE LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 3 - The Gut Microbiome Beyond the Bacteriome-The Neglected Role of Virome and Mycobiome in Health and Disease GENERAL FEATURES OF THE GUT MICROBIOME CORE GUT VIROME AND ITS PHYSIOLOGIC IMPORTANCE Inflammatory Responses Actions of the Gut Virome on the Host Genome CORE GUT MYCOBIOME AND ITS PHYSIOLOGIC ROLE Lifestyle and the Mycobiome Systemic Impact Fungal Virulence Yeast-to-Hyphae Transition ROLES IN DISEASE STATES Virus Latent State Commensal Fungi and Progression of Infectious Diseases Fungal Signature in Obesity and Inflammatory Bowel Disease Virome-Mycobiome Interactions Prophage-Bacteria-Host Synergy FUTURE ASPECTS OF THE MANIPULATION OF GUT VIROME AND GUT MYCOBIOME REFERENCES 4 - Techniques for Phenotyping the Gut Microbiota Metabolome METABOLOMICS IN THE CONTEXT OF SYSTEMS BIOLOGY WORKFLOW IN METABOLOMICS: TARGET ANALYSIS VERSUS FINGERPRINTING SAMPLING, COLLECTION, STORAGE, AND TRANSPORTATION FECAL COMPOSITION, METABOLITE ENRICHMENT, AND COMPLETE METABOLITE EXTRACTION CRITICAL ANALYSIS OF AVAILABLE METABOLOMIC TECHNIQUES DATA PROCESSING AND INTERPRETATION DATA VALIDATION DIAGNOSIS AND THERAPEUTIC IMPLICATIONS OF GUT MICROBIOTA METABOLITES ACKNOWLEDGMENTS REFERENCES 5 - Metabolomics Tools and Information Retrieval in Microbiome Hacking INTRODUCTION: WHAT IS METABOLOMICS? ANALYTICAL STRATEGIES: FROM BIOLOGICAL SAMPLES TO SIGNALS Experimental Design Considerations: Doing It Right From the Beginning Biological Samples Sample Preparation Analytical Platforms Nuclear Magnetic Resonance Spectroscopy: Capturing the Dance of Atoms Mass Spectrometry: Weighing the Moving Ions Hyphenated Mass Spectrometry Techniques Toward Real-Time MS-Based Metabolomics QUALITY CONTROL MANAGEMENT: CLEANING DATA TO GET CONSISTENT SIGNALS BIOLOGICAL INFORMATION RECOVERY: FROM DATA TO INFORMATION Preprocessing: Turning Signals Into Numbers Normalization, Transformation, and Scaling Data Analysis Univariate Data Analysis: One Variable at a Time Is Not Enough Multivariate Data Analysis: Consider It as a Whole Metabolite Annotation and Characterization Functional Analysis: Connecting the Dots HACKING THE HOST-MICROBIOME METABOLIC INTERACTIONS THROUGH METABOLOMICS AND BEYOND CONCLUSION REFERENCES 6 - Laboratory Simulators of the Colon Microbiome INTRODUCTION KEY MICROORGANISMS AND CRUCIAL METABOLITES GENERAL MODELS OF THE COLON MICROBIOME Batch Fermentation Models Dynamic Fermentation Models AUTOMATED SIMULATORS OF THE COLON MICROBIOME: THE SIMGI AND BFBL MODELS PROTOCOLS AND APPLICATIONS THERAPEUTICAL AND OTHER STRATEGICAL APPLICATIONS CONCLUDING REMARKS REFERENCES 7 - Potential of Metabolomics to Breath Tests INTRODUCTION Exhaled Breath Versus Exhaled Breath Condensate Technical Hurdles-Dilution and Standardization Airway Anatomy and Physiology LABORATORY EQUIPMENT FOR SAMPLING Industrialized Exhaled Breath Condensate Samplers Exhaled Breath Samplers Collection Routine CRUCIAL MOLECULES AND PATHWAYS Nitrogen Reactive Species Arachidonic Acid APPLICATIONS IN AIRWAY DISEASES Untargeted Versus Fingerprinting Metabolomics Cystic Fibrosis and Bacterial Pneumonia Ventilator-Associated Pneumonia APPLICATIONS IN LUNG CANCER Breath as Sample for LC Biomarkers Searching EBC as Sample for LC Biomarkers Searching Marker Interpretation, and Overlapping With Other tumors APPLICATIONS IN GASTROINTESTINAL AND SYSTEMIC DISEASES Microbial Fermentation and Inflammatory Bowel Disease Lipid Peroxidation and Oxidative Stress Type 2 Diabetes SENSORS FOR BREATH ANALYSIS Electronic Nose Quantum Cascade Laser Breath Analyzers CONCLUSIONS LIST OF ABBREVIATIONS REFERENCES II - Background Information 8 - Metabolome and Microbiome From Infancy to Elderly INTRODUCTION The Metabolome GUT MICROBIOME AND METABOLITES MICROBIOME AND METABOLOME ON INFANCY THE MICROBIOME AND METABOLOME IN HEALTHY ADULTS Microbiome and Metabolome in the Aging Process CONCLUSION REFERENCES 9 - The Oral Microbiome INTRODUCTION ORAL BIOFILMS COMPOSITION OF THE ORAL MICROBIOME Acquisition of the Oral Microbiome The Placenta and the Microbiome THE ORAL MICROBIOME OF THE INFANT AND CHILD The Oral Environment Oral Microenvironments BIOFILM ARCHITECTURE AND COOPERATION PATHOGENESIS OF SUPRAGINGIVAL BIOFILMS Is It Symbiosis or Dysbiosis? Oral Diseases The Caries Microbiome Bacterial Signature in Childhood Caries NEWLY IDENTIFIED BENEFICIAL AND PATHOGENIC MICROBES ACTIVE VERSUS INACTIVE BACTERIA Gum Microbiome Oral Mycobiome Oral Microbiome Associated With Systemic Disease CONCLUSIONS REFERENCES 10 - The Gastric Microbiome in Benign and Malignant Diseases THE GASTRIC MICROBIAL COMMUNITY TECHNICAL LIMITATIONS IN THE GASTRIC MICROBIOME ANALYSIS EUKARYOTES AND VIRUSES IN THE UPPER GASTROINTESTINAL TRACT HELICOBACTER PYLORI AND GASTRIC CANCER GENERAL DYSBIOSIS IN GASTRIC CANCER GASTRIC MICROORGANISMS AND EXTRAGASTRIC DISEASE EPSTEIN-BARR VIRUS AND GASTRIC CANCER LIFESTYLE HABITS AND STOMACH DYSBIOSIS CONCLUSIONS AND FUTURE PERSPECTIVES ACKNOWLEDGMENTS REFERENCES 11 - The Human Vaginal Microbiome INTRODUCTION NONPREGNANT WOMEN PREGNANT WOMEN INFLUENCE OF THE VAGINAL MICROBIOME ON MOTHER TO NEWBORN BACTERIAL TRANSMISSION LACTIC ACID MICROBIOME-EPITHELIAL CELL INTERACTIONS STRESS CAN VARIATIONS IN THE VAGINAL MICROBIOME BE EASILY DETECTED? CAN A WOMAN'S VAGINAL MICROBIOME BE ALTERED? WHAT ABOUT THE HOST? REFERENCES 12 - Bioactive Molecules of the Human Microbiome: Skin, Respiratory Tract, Intestine NATURAL PRODUCTS AS SOURCES OF BIOLOGICAL ACTIVITY THE HUMAN MICROBIOME AS A BLACK BOX FOR NATURAL PRODUCT DISCOVERY BIOACTIVE MOLECULES OF THE SKIN MICROBIOME Staphylococcus Propionebacterium acnes Corynebacterium BIOACTIVE MOLECULES OF THE RESPIRATORY TRACT MICROBIOME S. aureus Carriers Corynebacterium Moraxella catarrhalis BIOACTIVE MOLECULES OF THE GUT MICROBIOME Short-Chain Fatty Acids Microbiome Vitamins Quorum Sensing Biomolecules Bile Acid Metabolism Lantibiotics and Bacteriocins Microcins PRACTICAL APPLICATIONS AND CONCLUDING REMARKS REFERENCES 13 - Role of the Microbiome in Intestinal Barrier Function and Immune Defense THE HUMAN MICROBIOTA Intestinal Microbiota: A Functional Organ Key Commensals and Pathogens Colonization Resistance and Pathogen Inhibition METABOLITES AND PATHWAYS Short-Chain Fatty Acids Primary and Secondary Bile Acids Amino Acid and Choline Metabolites COMMENSALS AND MUCOSAL IMMUNITY: THE CROSSTALK AGAINST PATHOGENS Mucosal Anatomy The Gut as an Immune Organ Flagellin and Pathogenic Bacteria T-Cell Subsets T Regulatory Cells (Treg) Bacteriocins GUT MICROBIOTA MODULATION: A FOCUS ON THERAPIES Antibiotics Probiotics Prebiotics Synbiotics OTHER REPERCUSSIONS OF MUCOSAL IMMUNITY BACTERIAL TRANSLOCATION: JUST A THEORETICAL POSSIBILITY OR A REAL CAUSE OF SYSTEMIC INFECTION LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 14 - The Cross Talk Between Bile Acids and Intestinal Microbiota: Focus on Metabolic Diseases and Bariatric Surgery INTRODUCTION BILE ACID PHYSIOLOGY AND METABOLISM Secondary Bile Acids MICROBIAL BIOTRANSFORMATION OF BILE ACIDS Deconjugation Oxidation and Epimerization 7-α-Dehydroxylation Esterification BILE ACID EFFECTS ON INTESTINAL MICROBIOTA BILE ACIDS AS SIGNALING MOLECULES FARNESOID X RECEPTOR, OBESITY, AND GLUCOSE METABOLISM BILE ACIDS HEALTH EFFECTS, BARIATRIC SURGERY, AND MICROBIOTA BARIATRIC INTERVENTIONS CONCLUSIONS AND PERSPECTIVES REFERENCES III - Established and Experimental Interventions 15 - Use of Probiotics in Inflammatory Bowel Disease INFLAMMATORY BOWEL DISEASES RELEVANT MICROBIAL POPULATIONS Key Molecules and Signaling Pathways in IBD In Vitro and in Vivo Models METABOLOME, TRANSCRIPTOME, AND PROTEOME Metabolome Proteome Interfaces With Antibiotics and Other Drugs THERAPEUTIC PROTOCOLS Use of Probiotics in Ulcerative Colitis Use of Probiotics and Synbiotics in Crohn Disease Fecal Microbiota Transplantation/FMT DIET, NUTRITION, AND EXERCISE AS OTHER LIFESTYLE REPERCUSSIONS Diet and Nutrition Exercise, Physical Activity, and Lifestyle Repercussions REFERENCES 16 - Current Status of Fecal Microbiota Transplantation INTRODUCTION FECAL MICROBIOTA TRANSPLANTATION: REGULATORY ASPECTS FECAL MICROBIOTA TRANSPLANTATION PROCEDURE: PREPARATION, ADMINISTRATION Donor Selection PREPARATION OF FMT Delivery of FMT CURRENT INDICATION: TREATMENT OF RECURRENT FORMS OF CLOSTRIDIUM DIFFICILE INFECTIONS FMT BEYOND C. DIFFICILE: PERSPECTIVES FMT and Inflammatory Bowel Disease FMT and Irritable Bowel Syndrome FMT and Decolonization of Antibiotic-Resistant Bacteria in the Gastrointestinal Tract FMT and Other Indications CONCLUSION LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 17 - Effects of Probiotics on Improvement of Metabolic Factors in Pregnant Women: A Metaanalysis of Randomized Plac ... INTRODUCTION Obesity and Diabetes in Pregnancy Gestational Diabetes Mellitus Oxidative Stress Therapeutic Options in Gestational Diabetes Mellitus Literature Search Study Descriptions Effects on fasting Glucose Effects on Insulin Effects on Homoeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) Effects on Body Weight Effects on Triglycerides Effects on VLDL, TAC, and GSH COMMENTS Implications for Treatment and Future Research REFERENCES FURTHER READING 18 - Current Options for Fecal Transplantation in Clostridium difficile Infection INTRODUCTION RELEVANT MICROBIAL POPULATIONS CRUCIAL MOLECULES AND PATHWAYS Clostridium difficile Life Cycle Prevention of Colonization The Role of Secondary Bile Salts Colonization Resistance and Nutrient Limitation The Antiinflammatory Effect of the Normal Microbiome Normal Microbiota Produces Bactericidal Metabolites Short-Chain Fatty Acid Metabolism and Gut Epithelial Integrity Transfer of Bacteriophages INTERFACES WITH ANTIBIOTICS AND OTHER DRUGS DIAGNOSTIC TESTS THERAPEUTIC PROTOCOLS Treatment of Clostridium difficile Infection Fecal Microbial Transplantation Fecal Microbial Transplantation Protocol Selecting a Donor The Personalized Fecal Microbial Transplantation Procedure FMT FOR MAINSTREAM USE, AND THE FUTURE OF FECAL-BASED THERAPIES Stool-Substitute Therapies Use of Sterile Filtrates From Donor Stool Bacteriophage-Based Therapies Bacterial Spore-Based Therapies Probiotics for the Treatment of CDI CONCLUSION REFERENCES 19 - Targeted Delivery of Bacteriophages to the Gastrointestinal Tract and Their Controlled Release: Unleashing the ... INTRODUCTION Mucus-Associated Phages Safe Alternatives for Current Antibiotic Options Bioengineered Avirulent Bacteria Available Phage Families Phage Laboratory Processing Mechanism of Action Gastrointestinal Bacterial Infections ENCAPSULATION OF BACTERIOPHAGES Phage In Vitro Stability FREEZE DRYING OF BACTERIOPHAGES SPRAY DRYING OF BACTERIOPHAGES Other Technical Considerations METHODS USED FOR PHAGE ENCAPSULATION IN MICRO- AND NANOPARTICLE SOLID DOSAGE FORMS Phage Survival in the Upper Gastrointestinal Tract Acid pH Gastrointestinal Motility, Osmotic Gradient Phage Encapsulation Using Membrane Microarrays Microfluidic Microencapsulation CONCLUSIONS REFERENCES FURTHER READING 20 - The Unknown Effect of Antibiotic-Induced Dysbiosis on the Gut Microbiota INTRODUCTION BACTERIAL BIOFILMS ANTIBIOTIC ADMINISTRATION ANTIBIOTIC SPECTRUM BACTERIAL DIVERSITY PROTEOBACTERIA OVERGROWTH ANTIBIOTIC-INDEPENDENT LOSS OF DIVERSITY BACTERIAL CROSS TALK ANTIBIOTIC THERAPY OF INTESTINAL DYSBIOSIS ANTIBIOTICS IN URINARY INFECTION THE URINARY MICROBIOME URINARY VERSUS GASTROINTESTINAL DYSBIOSIS NON-ANTIBIOTIC MANAGEMENT OF DYSBIOSIS PROBIOTICS PREBIOTICS FECAL TRANSPLANTS ECOSYSTEM EVALUATION MULTIOMICS INVESTIGATION DIAGNOSTIC OPTIONS ONGOING STUDIES ACKNOWLEDGMENTS REFERENCES 21 - The Myth and Therapeutic Potentials of Postbiotics INTRODUCTION Alternatives Without Live Bacteria KEY POSTBIOTIC PRODUCER CELLS POSTBIOTIC PRODUCTION CHARACTERISTICS AND FUNCTIONALITY OF POSTBIOTICS THERAPEUTIC POSSIBILITIES OF POSTBIOTICS Malignant Diseases Additional Anticancer Molecules POTENTIAL OF POSTBIOTIC INTERFACES WITH ANTIBIOTICS AND OTHER DRUGS Antibiotic Replacement Improvement of Gut Microenvironment Inhibition of Hypercholesterolemia POTENTIAL APPLICATION OF POSTBIOTIC IN DISEASE PREVENTION Intestinal Infections Inflammation and Immune Response THE WAY FORWARD OF POSTBIOTIC APPLICATIONS Postbiotics as Alternative/Complementary/Integrative Treatment for Cancers Postbiotics as Antioxidants LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES IV - Diagnostic and Therapeutical Applications 22 - The Microbiome and Metabolome in Metabolic Syndrome RELEVANT MICROBIAL POPULATIONS IN VIVO MODELS METABOLOME AND PROTEOME Amino Acid Metabolism Lipid Metabolism Carbohydrate Metabolism CRUCIAL MOLECULES AND PATHWAYS The LPS-CD14 Complex Induces NF-κB The Influence of CD4 T Cells Through RORγt Expression The Farnesoid X-Activated Receptor and the Bile Acid ``Cross Talk'' INTERFACES WITH ANTIBIOTICS THERAPEUTICAL PROTOCOLS AND DISEASE PREVENTION DIET, NUTRITION, EXERCISE, AND OTHER LIFESTYLE REPERCUSSIONS FINAL CONSIDERATIONS ACKNOWLEDGMENTS REFERENCES 23 - The Gut Microbiota as a Therapeutic Approach for Obesity INTRODUCTION: THE GUT MICROBIOME AND OBESITY THE MULTIFACTORIAL ASSOCIATIONS BETWEEN THE MICROBIOTA AND THE HOST Can We Identify an Obese Microbiota? Proposed Cellular and Molecular Mechanisms for the Potential Link Between Microbiota and Obesity Intestinal Dysbiosis Anti-inflammatory Nutrients and Obesity Studying the Gut Metabolome in Obesity Bariatric Surgery Metabolic Markers Related to Carbohydrate and Amino Acid MICROBIOTA-BASED THERAPEUTIC APPROACHES Antibiotics and Obesity Phage Therapy Naturally Occurring Dietary Compounds, Obesity, and the Microbiome Fecal Microbiota Transplantation CONCLUSIONS LIST OF ACRONYMS AND ABBREVIATIONS ACKNOWLEDGMENTS REFERENCES 24 - The Gut Microbiome After Bariatric Surgery INTRODUCTION HORMONE-MEDIATED WEIGHT LOSS IN BARIATRIC SURGERY THE INTESTINAL MICROBIOME MICROBIOME DYSBIOSIS AND OBESITY Individual Markers of Obesity GUT MICROBIOME AND BARIATRIC SURGERY Microbiome Signature of Gastric Bypass Operation FINGERPRINTING SLEEVE GASTRECTOMY CONTRIBUTION OF BILE ACIDS CONCLUSIONS AND FUTURE DIRECTIONS ACKNOWLEDGMENTS REFERENCES FURTHER READING 25 - Gut Dysbiosis in Arterial Hypertension: A Candidate Therapeutic Target for Blood Pressure Management INTRODUCTION GUT DYSBIOSIS AND ARTERIAL HYPERTENSION Metagenomic Studies The Metabolome and Short-Chain Fatty Acids Transcriptomic Investigation TRIMETHYLAMINE N-OXIDE AND CARDIOVASCULAR FUNCTION Protein Metabolites Proinflammatory Environment Evidence Relating Probiotic Effects on Blood Pressure Evidence Relating Prebiotic Effects on the Blood Pressure Evidence Relating Synbiotic Effects on Blood Pressure CONCLUSION LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES FURTHER READING 26 - The Emerging Role of Microbiome-Gut-Brain Axis in Functional Gastrointestinal Disorders ROME IV CRITERIA AND FUNCTIONAL GASTROINTESTINAL DISORDERS MICROBIOTA AND INTESTINAL BARRIER Functional Gastrointestinal Disorder Pathophysiology GUT-BRAIN AXIS Nerves, Neurotransmitters, and Hormones FUNCTIONAL GASTROINTESTINAL DISORDERS AND INTESTINAL BARRIER DISRUPTIONS Antibiotic Prescriptions Contribution of Probiotics Symptom-Related Signatures Intestinal Permeability and Leaky Gut Altered Immunoinflammatory Profile MANAGEMENT AND RECOMMENDATIONS Dietary Modifications Probiotics Probiotic Metaanalyses Pharmacological Approach Faecal Microbiota Transplantation LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 27 - The Microbiome and Metabolome in Nonalcoholic Fatty Liver Disease INTRODUCTION Gut-Liver Axis INTESTINAL ENVIRONMENT Endotoxin and Liver Inflammation Intestinal Inflammasomes Bile Acids and Farnesoid X Receptor Gut Microbiome in NAFLD Patients Response to High-Fat Diet SIBO AND INCREASED INTESTINAL PERMEABILITY IN NAFLD PATIENTS USE OF PROBIOTICS AND SYNBIOTICS IN NAFLD PATIENTS CONCLUSIONS REFERENCES 28 - The Microbiome and Metabolome in Alcoholic Liver Disease INTRODUCTION GUT-LIVER AXIS Communication Between the Liver and Intestine The Intestinal Microbiota Gut Barrier Function ALCOHOL AND THE INTESTINAL MICROBIOME Alterations of Gut Microbiome and Metabolome Alcohol and Liver Disease Leaky Gut Gut-Derived Bacterial Products and Liver Injury Immune Dysfunction Other Factors Contributing to Alcoholic Liver Disease IN VITRO AND IN VIVO MODELS METABOLOME, TRANSCRIPTOME, AND PROTEOME THERAPEUTIC PROTOCOLS (PROBIOTICS, PREBIOTICS, SYNBIOTICS, FECAL TRANSPLANT) Probiotics Prebiotics Synbiotics Fecal Microbiota Transplant Antibiotics OTHER STRATEGICAL INTERVENTIONS LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 29 - The Microbiome, Metabolome, and Proteome in Preterm Neonatal Sepsis OVERVIEW MICROBIOME Role of the Microbiome in Early Onset Sepsis Role of the Microbiome in Late Onset Sepsis Potential of Specific Organisms to Prevent Bacterial Translocation in Preterm Infants METABOLOMIC AND PROTEOMIC BIOMARKERS OF SEPSIS Urine Metabolome Stool Metabolome Serum Proteome and Metabolome CONCLUSION REFERENCES 30 - Gut Microbiome in the Elderly Hospitalized Patient: A Marker of Disease and Prognosis? AGING AND GUT MICROBIOTA: A CLINICAL PERSPECTIVE GUT MICROBIOTA DURING HOSPITALIZATION: THE INTENSIVE CARE UNIT GUT MICROBIOTA DURING HOSPITALIZATION: THE MEDICAL AND GERIATRIC UNIT THE CLINICAL RELEVANCE OF GUT MICROBIOTA ALTERATIONS IN HOSPITAL GUT MICROBIOTA MANIPULATIONS IN HOSPITALIZED OLDER INDIVIDUALS FUTURE PERSPECTIVES: GUT MICROBIOTA AND TRAJECTORIES OF AGING REFERENCES 31 - The Lung Microbiome, Metabolome, and Breath Volatolome in the Diagnosis of Pulmonary Disease INTRODUCTION THE LUNG MICROBIOTA THE INTERACTION BETWEEN THE LUNG MICROBIOTA AND THE IMMUNE SYSTEM THE INDIGENOUS COMMUNITY AND INVASIVE PATHOGENS THE DYNAMICS OF LUNG MICROBIOTA PROFILES IN RESPIRATORY FUNGAL DISEASE Chronic Obstructive Pulmonary Disease Cystic Fibrosis P. aeruginosa and A. fumigatus Coinfection Asthma THE MICROBIOTA-METABOLOME CROSSTALK IN RESPIRATORY FUNGAL DISEASES METABOLOMIC PROFILING IN FUNGAL DIAGNOSTICS Fungal Breath Fingerprinting (VOCs) THE CLINICAL APPLICATION OF THE MICROBIOTA-METABOLOME CROSSTALK CONCLUDING REMARKS ACKNOWLEDGMENTS REFERENCES 32 - The Oral, Genital and Gut Microbiome in HIV Infection INTRODUCTION HIV INFECTION AND MICROBIOTA Alterations of Microbiota at the Genital and Rectal Sites in HIV-Infection Alterations of Microbiota in Blood, Semen, and Brain in HIV Infection Alterations of Microbiota in Oral Cavity and Airways in HIV Infection Bacterial Translocation and Alterations of Gut Microbiota in HIV Infection Gut Microbiota Composition: Bacterial Diversity/Richness Microbial Composition Influence of ART HIV Infection and Virome HIV INFECTION, METABOLIC PATHWAYS, AND MICROBE-ASSOCIATED METABOLITES Metabolic Pathways and Microbe-Associated Metabolites in HIV DIAGNOSTIC IMPLICATIONS THERAPEUTICAL APPROACHES Probiotics Effects on CD4, Microbial Translocation, and Inflammation Effects on Diarrhea Effects on Bacterial Vaginosis Other Effects Side Effects Prebiotics Symbiosis Between Probiotics and Prebiotics Fecal Bacteriotherapy or Fecal Transplantation (FMT) Other Interventions CONCLUSIONS LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 33 - The Gut Microbiome in Autoimmune Diseases GUT MICROBIOME AND AUTOIMMUNE DISEASES MULTIPLE SCLEROSIS PROBIOTICS IN MULTIPLE SCLEROSIS Type 1 Diabetes/T1D PROBIOTICS IN T1D RHEUMATOID ARTHRITIS PROBIOTICS IN RHEUMATOID ARTHRITIS SYSTEMIC LUPUS ERYTHEMATOSUS PROBIOTICS IN SLE CONCLUSIONS REFERENCES 34 - The Gut Microbiome and Metabolome in Multiple Sclerosis INTRODUCTION GUT MICROBIOTA MS AND THE GUT MICROBIOTA GUT MICROBIOTA AND MODULATION OF THE IMMUNE RESPONSE Bacterial Fingerprint Short-Chain Fatty Acids THE GUT MICROBIOTA AND METABOLIC PATHWAYS Regulatory T cells Phytoestrogens Tryptophan and Indole Metabolites Bile Acid Metabolism Human Studies With Bile Acids THE INTERFACE BETWEEN THE GUT MICROBIOTA AND PHARMACEUTICAL AGENTS DIAGNOSTIC IMPLICATIONS Diagnostic and Therapeutic Potential of Gut Metabolites USE OF GUT BACTERIA AS POTENTIAL THERAPEUTIC AGENTS Fecal Microbiota Transplantation/FMT DIET AND THE GUT MICROBIOTA CONCLUSION REFERENCES 35 - Connections Between Gut Microbiota and Bone Health INTRODUCTION MOLECULES AND PATHWAYS GM, IMMUNE SYSTEM, AND BONE LOSS GM AND BONE HEALTH BEYOND IMMUNE SYSTEM GM MANIPULATION AND BONE HEALTH FUTURE PERSPECTIVES LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 36 - The Gut Microbiome in Chronic Kidney Disease INTRODUCTION CKD ALTERING THE GUT ECOSYSTEM DISTURBED GUT ECOSYSTEM AS A CATALYZER FOR CKD METABOLIC DISORDERS THERAPEUTIC APPROACHES Oral Adsorbents Prebiotics Probiotics Synbiotics Low-Protein Diet Physical Exercise CONCLUSION LIST OF ABBREVIATIONS REFERENCES 37 - Dysbiosis in Benign and Malignant Diseases of the Exocrine Pancreas INTRODUCTION THE MICROBIOME AND ``OMICS'' TOOLS CLINICAL IMPLICATIONS OF DYSBIOSIS SMALL BOWEL BACTERIAL OVERGROWTH IN CHRONIC PANCREATITIS RELEVANT MICROBIAL POPULATIONS Acute Pancreatitis Chronic Pancreatitis Pancreatic Ductal Cancer H. PYLORI AND PDC CRUCIAL MOLECULES AND PATHWAYS EXCESSIVE PROINFLAMMATORY ENTEROBACTERIA CHRONIC INFLAMMATION AND CARCINOGENESIS ALCOHOLIC DYSBIOSIS IN VITRO AND IN VIVO MODELS CLINICAL IMPLICATIONS ANTIBIOTICS VERSUS PROBIOTICS CONCLUSIONS REFERENCES 38 - Importance of the Microbiome and the Metabolome in Cancer MICROBES ASSOCIATED WITH CARCINOGENESIS Colorectal Cancer Gastric Cancer Oral Cancer MICROBIAL METABOLOME AND CANCER Detrimental Metabolites Beneficial Metabolites EXPERIMENTAL MODELS TO EVALUATE THE MICROBIAL METABOLOME INFLUENCE IN CANCER MICROBIOME ALTERATION AND METABOLOME: INTERFACE OF ANTIBIOTICS AND OTHER DRUGS IN CANCER DIAGNOSTIC IMPLICATIONS THERAPEUTICAL PROTOCOLS Probiotics DIET, NUTRITION, EXERCISE, OTHER LIFESTYLE REPERCUSSIONS, AND PREVENTION Diet and Exercise Obesity Alcohol and Tobacco LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 39 - The Microbiome in Graft Versus Host Disease INTRODUCTION GRAFT-VERSUS-HOST DISEASE Diagnosis Pathophysiology Prevention and Treatment GUT MICROBIOTA AND AGVHD Antibiotics and Decontamination Dysbiosis and aGVHD Short-Chain Fatty Acids and aGVHD Antimicrobial Peptides and aGVHD MICROBIOTA AND POSTTRANSPLANT MORTALITY FECAL MICROBIOTA TRANSPLANTATION: A NEW TREATMENT? CONCLUSIONS LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES 40 - Impact of the Gut Microbiome on Behavior and Emotions INTRODUCTION BRAIN STRUCTURES INVOLVED IN BEHAVIOR AND EMOTIONS GUT-BRAIN AXIS THE LINK BETWEEN MICROBIOTA, BEHAVIOR, AND EMOTIONS Gastrointestinal Disorders and Emotions Psychiatric and Social Behavior Disorders Gut Microbiota and Emotional Disorders Eating Behavior PSYCHOBIOTICS: FROM PREBIOTICS AND PROBIOTICS TO DIETARY INTERVENTIONS Healthy Diets and Supplements Ethnic and Geographical Considerations CONCLUSION LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES FURTHER READING V - Applications for Foods, Drugs, and Xenobiotics 41 - The Gut Microbiome in Vegetarians INTRODUCTION GUT MICROBIOME-MODULATED EFFECTS OF DIETARY COMPONENTS Carbohydrates Fatty Acids Proteins Phytochemicals RELATIONSHIP OF DIETARY PATTERNS, GUT MICROBIOME, AND CHRONIC DISEASES BACTERIAL ENTEROTYPES LIST OF ABBREVIATIONS GLOSSARY REFERENCES FURTHER READING 42 - Metformin: A Candidate Drug to Control the Epidemic of Diabetes and Obesity by Way of Gut Microbiome Modification MULTIFACTORIAL PATHOGENESIS OF OBESITY Inflammation, Obesity, and Insulin Resistance Insulin Signaling in Hepatocytes Other Organs and Tissues GUT MICROBIOME: CAUSE OR EFFECT OF OBESITY? Divergent Results Dietary Influences Host Genes and Microbiome Composition The Gut Metabolome in Obesity: Role of Short Chain Fatty Acids Host Microbiome Cross Talk Immunoinflammatory Activation MICROBIOME MODULATION AND CONTROL OF OBESITY METFORMIN AND GUT MICROBIOME METFORMIN IN OBESITY AND DIABETES Metformin-Microbiome Antiobesity Link CONCLUSIONS DISCLAIMER REFERENCES FURTHER READING 43 - Deleterious Impact of Smog on the Intestinal Bacteria INTRODUCTION WHAT IS SMOG AND HOW POLLUTANTS ENTER INTO THE GUT? ECOLOGY OF THE GUT MICROBIOTA Bacterial Consortia and Metabolic Synergy Spatial Organization and Resource Sharing Agonism and Antagonism in the Gut Environment SUCCESSION OF GUT MICROBIOTA SMOG-INDUCED OXIDATIVE STRESS IN BACTERIA Lipid Peroxidation Electron Transfer Reactions and Transition Metals Nitrogen Oxides Sulfur Dioxide Particulate Matter Volatile Organic Compounds SMOG CAN INDUCE INFLAMMATION PERSPECTIVE REFERENCES FURTHER READING VI - Challenges and Promises for the Future 44 - New-Generation Probiotics: Perspectives and Applications INTRODUCTION NEXT-GENERATION PROBIOTICS EXPERIMENTAL AND CLINICAL STUDIES Akkermansia muciniphila MECHANISM OF ACTION Faecalibacterium prausnitzii MECHANISM OF ACTION Bacteroides spp. Eubacterium halli Clostridium Clusters PRODUCTION CONSTRAINTS SAFETY ASPECTS OF NGPS CONCLUSION AND FUTURE DIRECTIONS REFERENCES 45 - Fecal Microbiota Transfer and Inflammatory Bowel Disease: A Therapy or Risk? INTRODUCTION INVESTIGATING THE MICROBIOME: THE OMICS ERA Healthy Intestinal Microbiome Alterations of Bacterial Populations in Inflammatory Bowel Disease Diminished Protective Bacteria Increased Pathogenic Bacteria Crohn's Disease Precipitating Agents Contribution of Proteobacteria Pathobionts Further Implications FECAL MICROBIOTA TRANSPLANTATION IN INFLAMMATORY BOWEL DISEASE Ulcerative Colitis Crohn's Disease SAFETY TECHNICAL CHALLENGES, FUTURE CONSIDERATIONS, AND NEXT-GENERATION FECAL MICROBIOTA TRANSPLANTATION Donor Screening and Selection Formulation of Fecal Samples Route of Delivery Frequency of Delivery Engraftment CONCLUSIONS LIST OF ACRONYMS AND ABBREVIATIONS REFERENCES FURTHER READING 46 - Precision Medicine: the Microbiome and Metabolome INTRODUCTION Pharmacogenetics, Pharmacogenomics, Pharmacometabolomics Bacterial Genomics Molecular Pathology Precision Medicine and Metabolomic Signatures MICROBIOME SIGNATURES Nonalcoholic Fatty Liver Disease Alcoholic Hepatitis and Liver Cirrhosis Cancer Crohn's Disease Obesity and Diabetes Atherosclerotic Cardiovascular Disease Arterial Hypertension Rheumatological and Autoimmune Conditions Gut Dysbiosis Point-of-care microbiomics: ``Gut on a chip'' METABOLOMIC FINGERPRINTING Obesity and NAFLD Diabetes Longevity Cancer Cancer Chemotherapy and Immunotherapy Atherosclerosis Intestinal Barrier Function VOLATILE ORGANIC COMPOUNDS AND THE ELECTRONIC NOSE Obesity and NAFLD Inflammatory Bowel Disease Cancer Lung Diseases LIPIDOME Multiple Sclerosis Obesity and Diabetes PROTEOME Obesity Inflammatory Bowel Disease GENETICALLY ENGINEERED MICROORGANISMS FINAL CONSIDERATIONS REFERENCES Microbiome and Metabolome Glossary FURTHER READING Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Back Cover