Principles in Microbiome Engineering Provides an overview of the techniques and applications insight into the complex composition and interactions of microbiomes Microbiomes, the communities of microorganisms that inhabit specific ecosystems or organisms, can be engineered to modify the structure of microbiota and reestablish ecological balance. In recent years, a better understanding of microbial composition and host-microbe interactions has led to the development of new applications for improving human health and increasing agricultural productivity and quality. Principles in Microbiome Engineering introduces readers to the tools and applications involved in manipulating the composition of a microbial community to improve the function of an eco-system. Covering a range of key topics, this up-to-date volume discusses current research in areas such as microbiome-based therapeutics for human diseases, crop plant breeding, animal husbandry, soil engineering, food and beverage applications, and more. Divided into three sections, the text first describes the critical roles of systems biology, synthetic biology, computer modelling, and machine learning in microbiome engineering. Next, the volume explores various state-of-the-art applications, including cancer immunotherapy and prevention of diseases associated with the human microbiome, followed by a concluding section offering perspectives on the future of microbiome engineering and potential applications. Introduces a variety of applications of microbiome engineering in the fields of medicine, agriculture, and food and beverage products Presents current research into the complex interactions and relationships between microbiomes and biotic and abiotic elements of their environments Examines the use of technologies such as Artificial Intelligence (AI), Machine Learning (ML), and Big Data analytics to advance understanding of microbiomes Discusses the engineering of microbiomes to address human health conditions such as neuro psychiatric disorders and autoimmune and inflammatory diseases Edited and authored by leading researchers in the rapidly evolving field, Principles in Microbiome Engineering is an essential resource for biotechnologists, biochemists, microbiologists, pharmacologists, and practitioners working in the biotechnology and pharmaceutical industries. Cover Title Page Copyright Contents Preface 1 Diet‐Based Microbiome Modulation: You are What You Eat 1.1 Introduction 1.1.1 Microbiome Diversity in Human Body 1.1.1.1 Oral Microbiome 1.1.1.2 Gastrointestinal Microbiome 1.1.1.3 Skin Microbiome 1.1.1.4 Respiratory Microbiome 1.1.1.5 Urogenital Microbiome 1.1.2 Elements that Influence Microbiome Development 1.1.2.1 Prebiotics 1.1.2.2 Probiotics 1.1.2.3 Diet and Nutrition 1.1.3 Current Approaches Employed in Studying the Human Microbiome 1.2 Dietary Lifestyle Variation Affecting Host Microbiome 1.2.1 Dietary Role in Shaping the Microbiome 1.2.1.1 Protein and Polypeptides 1.2.1.2 Soluble Saccharides 1.2.1.3 Dietary Fibers 1.2.1.4 Lipids 1.2.2 The Socioeconomic Impact on Diet‐Related Microbiome Changes 1.2.3 Age Groups and Dietary‐Related Microbiome Changes 1.2.4 Continental Dietary Difference and Its Effect of the Local Microbiome 1.2.4.1 Asia 1.2.4.2 Europe 1.2.4.3 Australia 1.2.4.4 Africa 1.2.4.5 South America 1.2.4.6 North America 1.3 Dietary Modulation of Microbiome for Disease Treatment 1.3.1 Infection 1.3.1.1 Fecal Microbiota Transplantation (FMT) 1.3.1.2 Prebiotic‐, Diet‐, and Probiotic‐Mediated Prevention of Pathogenic Infections 1.3.2 Inflammatory Disease 1.3.3 Cancer 1.3.4 Psychological Disease 1.3.4.1 Autism Spectrum Disorder 1.3.4.2 Neurodegenerative Diseases 1.3.5 Metabolic Disorder 1.3.5.1 Obesity 1.3.5.2 Diabetes 1.3.5.3 Non‐alcoholic Fatty Liver Disease (NAFLD) 1.4 Challenges and Opportunities 1.4.1 Limitations in the Field 1.4.2 Current Microbiome Project Supporting Infrastructures 1.4.2.1 International and Local Initiatives 1.4.2.2 Global Foundations 1.5 Concluding Remarks Acknowledgments References 2 Microbiome Engineering for Metabolic Disorders 2.1 Introduction 2.2 Microbiome Engineering for Diabetes and Obesity 2.2.1 Microbiome Engineering for the Hypoglycemic Effect to Treat Diabetes and Obesity 2.2.2 Microbiome Engineering for Immune Modulation to Treat Diabetes 2.3 Microbiome Engineering to Modulate Gut–Liver Axis 2.3.1 Microbiome Engineering to Modulate Ammonia Metabolism 2.3.2 Microbiome Engineering to Modulate Phenylalanine Metabolism 2.3.3 Microbiome Engineering to Modulate Bile‐Salt Metabolism 2.3.4 Microbiome Engineering to Modulate Fat Metabolism 2.4 Microbiome Engineering for Cardiovascular Diseases 2.4.1 Gut Microbiome Interventions for Cardiovascular Diseases 2.4.2 Role of Microbiome‐Derived TMAO in Cardiovascular Diseases 2.5 Microbiome Engineering to Modulate Gut–Brain Axis 2.5.1 Exploratory Studies on the Development of Psychobiotics 2.6 Clinical Translation of Live Biotherapeutic Products 2.7 Conclusion and Future Directions References 3 Repurposing Microbes for Therapeutic Applications in Humans 3.1 Introduction 3.2 A Brief Overview of Microbiota and Human Health 3.2.1 Interactions Between Microbes and Their Compositions Affect the Host Metabolic Status 3.2.2 Host–Microbe Interactions Constitute an Essential Part of Host Metabolism 3.3 Systems Biology Approach to Analyze the Gut Microbiota Functions 3.3.1 Rational Design of Gut Microbiome Editing Strategies 3.3.2 High‐Throughput Data‐Driven Understanding of Gut Microbiota 3.4 Engineering Microbiome to Treat Diseases 3.4.1 Strain Selection for Microbiome Engineering 3.4.2 Engineering Microbes to Sense and Respond to Disease‐Related Perturbations 3.4.3 Engineering Microbes to Express Therapeutic Proteins for Disease Treatment 3.5 Perspectives and Conclusion References 4 Modulating Residence Time and Biogeography of Engineered Probiotics 4.1 Introduction 4.2 Adhesion Mechanisms 4.3 Adhesion Modulation 4.4 Functional Encapsulations and Biofilms that Modify Gastrointestinal Dynamics of Probiotics 4.5 Metabolic Engineering to Modulate Gut Adaptation 4.6 Conclusions References 5 Microbiome Engineering for Next‐Generation Precision Agriculture 5.1 Background 5.2 Systems Approach to Microbiome Engineering 5.2.1 DBTL Framework for Microbiome Engineering 5.2.2 Computational Tools for Robust Microbiome Engineering 5.2.3 Genome‐Scale Metabolic Modeling 5.3 Synthetic Biology for Genome and Genetic Engineering of Phytobiomes 5.4 Conclusion and Future Perspectives Acknowledgments References 6 Biological Sensors for Microbiome Diagnostics 6.1 Introduction 6.1.1 The Malleable Microbiome 6.1.2 Engineered Probiotics 6.2 Diagnosing the Microbiome 6.2.1 Microbiome Analyses 6.2.1.1 Small Subunit rRNA Analysis 6.2.1.2 Metagenomics and Metatranscriptomics 6.2.1.3 Proteomics and Metabolomics 6.2.2 Considerations and Future of Microbiome Diagnosis 6.3 Types of Biosensors 6.3.1 Riboswitches 6.3.1.1 Riboswitches and Their Regulatory Mechanisms 6.3.1.2 Design and Selection of Synthetic Riboswitches 6.3.1.3 Riboswitches in Molecular Detection of Microbiome Metabolites 6.3.2 Transcription Factors 6.3.2.1 Transcription Factor Mining 6.3.2.2 Engineering Transcription Factors 6.3.2.3 Applications of Transcription Factors 6.3.3 Two‐Component Systems 6.3.3.1 Introduction to Two‐Component Systems 6.3.3.2 Expression of Natural TCS Systems for Gut Diagnostics 6.3.3.3 Engineering TCS‐Based Sensors for the Microbiome 6.3.4 G Protein‐Coupled Receptors 6.3.4.1 GPCRs and the Gut Microbiome 6.3.4.2 GPCRs Engineered Into Yeast 6.3.4.3 Recent Advances in Yeast GPCR‐Based Sensors 6.4 Testing and Utilizing Engineered Biosensors 6.4.1 Cell‐Free Protein Expression Systems (CFPS) for Biosensing 6.4.2 In Vitro Testing 6.4.2.1 In Vitro Models 6.4.2.2 Organ‐on‐a‐Chip 6.4.2.3 In Vitro Host–Microbe Characterization 6.4.3 Examples of Engineered Microbes 6.4.3.1 Identifying Microbiome Changes In Situ 6.4.3.2 Engineered Microbes for Disease Diagnostics 6.4.3.3 Cancer 6.4.3.4 Inflammatory Bowel Disease 6.4.3.5 Infection 6.4.3.6 Future Translation 6.5 Conclusions/Summary Acknowledgments References 7 Principles, Tools, and Applications of Synthetic Consortia Toward Microbiome Engineering 7.1 Introduction 7.2 Advantages of Labor Division via Synthetic Microbial Consortia 7.2.1 Providing Optimal Conditions 7.2.2 Reducing the Metabolic Burden on the Host 7.2.3 Reducing Crosstalk and Competition Within Synthetic Pathways 7.3 Tools for Engineering Synthetic Consortia 7.3.1 Genetic Manipulation Tools 7.3.2 Cell‐to‐Cell Communication 7.3.3 External and Intercellular Signal Molecules for Regulating Gene Expression and Population Composition 7.3.4 Secretion and Exchange of Metabolites 7.3.5 Analysis Tools 7.3.6 Computational Models 7.3.6.1 Dynamic/Deterministic Models 7.3.6.2 Agent‐Based Models 7.3.6.3 Stoichiometric and Genome‐Scale Metabolic Models 7.4 Engineering Syntrophy 7.5 Engineering Population Control 7.6 Synthetic Microbial Consortia and the Human Microbiome 7.7 Conclusions and Future Perspectives References 8 Fecal Microbiota Transplantation for Microbiome Modulation: A Clinical View 8.1 Introduction 8.2 Fecal Microbiota Transplantation (FMT) 8.2.1 Recruitment of Potential Donors 8.2.2 Administration of FMT 8.2.3 Safety 8.3 Clinical Application of Fecal Microbiota Therapy 8.3.1 C. difficile Infection (CDI) 8.3.2 Inflammatory Bowel Disease 8.3.3 FMT as a Therapeutic Option to Eradicate Highly Drug‐Resistant Enteric Bacteria Carriage 8.3.4 FMT and Irritable Bowel Syndrome 8.3.5 FMT and Slow‐Transit Constipation 8.3.6 FMT and Liver Diseases 8.4 FMT – Novel Indications 8.4.1 Chemotherapy‐Induced Diarrhea 8.4.2 Obesity and Metabolic Syndrome 8.4.3 Graft‐versus‐Host Disease (GvHD) 8.4.4 Autoimmune Diseases 8.4.5 Neuropsychiatric Disorders 8.5 Conclusion References 9 Maternal Microbiota as a Therapeutic Target 9.1 Introduction 9.2 Human Maternal Microbiota 9.2.1 Oral Microbiota 9.2.2 Vaginal Microbiota 9.2.3 Endometrial Microbiome 9.2.4 Gut Microbiome 9.2.4.1 Maternal Gut Microbiome and Immune Functions 9.2.4.2 Gut and Brain Axis 9.2.4.3 Epigenetic Regulation of Gut Microbiota 9.2.5 Placental Microbime and Meconium 9.3 Maternal Microbiota and Health 9.3.1 Developmental Origins of Adult‐Onset Diseases: Barker Hypothesis 9.3.2 Maternal Microbiota and Obesity 9.3.2.1 Maternal Diet and Gut Microbiota 9.3.2.2 Body Mass Index, Insulin Resistance, and Obesity in Pregnancy 9.3.2.3 Childhood Obesity 9.3.3 Miscarriages and Microbiome 9.3.4 Postpartum Microbiome 9.3.4.1 Mode of Delivery 9.3.4.2 Vaginal Seeding 9.3.5 Maternal Microbiota and Gestational Age at Birth 9.3.6 Maternal Microbiota and Maternal Inflammation and Intrauterine Infections 9.4 Human Milk Microbiota and Infant Health 9.5 Drug Treatment, Unhealthy Conditions, and Microbiome 9.5.1 Perinatal Antibiotic Treatment 9.5.2 Smoking 9.5.3 Stress Under Pregnancy 9.5.4 Autism Spectrum Disorders 9.5.5 Critical Illness of Newborns 9.6 Probiotic and Prebiotic Therapies as Modulators of Microbiome References 10 Transcription Factor‐Based Biosensors and Their Application in Microbiome Engineering Summary 10.1 Design: TF‐Based Biosensors 10.1.1 Transcriptional Repressors 10.1.2 Transcriptional Activators 10.1.3 One‐Component Regulatory System or Two‐Component Regulatory System 10.1.4 Types of Output Modules 10.1.5 Layered Genetic Circuits 10.2 Build: TF‐Based Biosensors 10.2.1 Construction of Genetic Circuits 10.2.1.1 Gene Synthesis 10.2.1.2 Restriction Enzyme–Based Cloning 10.2.1.3 Gibson Assembly 10.2.2 Chassis 10.3 Test: TF‐Based Biosensors Application in Microbiome 10.3.1 Diagnostics 10.3.2 Therapeutics 10.3.3 Biocontainment 10.4 Learn: Strategies for TF‐Based Biosensor Improvement 10.5 Conclusions Acknowledgments References Index EULA