Examining the enormous potential of microbiome manipulation to improve health

Associations between the composition of the intestinal microbiome and many human diseases, including inflammatory bowel disease, cardiovascular disease, metabolic disorders, and cancer, have been elegantly described in the past decade. Now, whole-genome sequencing, bioinformatics, and precision gene-editing techniques are being combined with centuries-old therapies, such as fecal microbiota transplantation, to translate current research into new diagnostics and therapeutics to treat complex diseases.Bugs as Drugs provides a much-needed overview of microbes in therapies and will serve as an excellent resource for scientists and clinicians as they carry out research and clinical studies on investigating the roles the microbiota plays in health and disease.

InBugs as Drugs, editors Robert A. Britton and Patrice D. Cani have assembled a fascinating collection of reviews that chart the history, current efforts, and future prospects of using microorganisms to fight disease and improve health. Sections cover traditional uses of probiotics, next-generation microbial therapeutics, controlling infectious diseases, and indirect strategies for manipulating the host microbiome. Topics presented include:

How well-established probiotics support and improve host health by improving the composition of the intestinal microbiota of the host and by modulating the host immune response.The use of gene editing and recombinant DNA techniques to create tailored probiotics and to characterize next-generation beneficial microbes. For example, engineering that improves the anti-inflammatory profile of probiotics can reduce the number of colonic polyps formed, and lactobacilli can be transformed into targeted delivery systems carrying therapeutic proteins or bioengineered bacteriophage.The association of specific microbiota composition with colorectal cancer, liver diseases, osteoporosis, and inflammatory bowel disease. The gut microbiota has been proposed to serve as an organ involved in regulation of inflammation, immune function, and energy homeostasis.Fecal microbiota transplantation as a promising treatment for numerous diseases beyond C. difficile infection. Practical considerations for using fecal microbiota transplantation are provided, while it is acknowledged that more high-quality evidence is needed to ascertain the importance of strain specificity in positive treatment outcomes.

Because systems biology approaches and synthetic engineering of microbes are now high-throughput and cost-effective, a much wider range of therapeutic possibilities can be explored and vetted.

If you are looking for online access to the latest clinical microbiology content, please visitwww.wiley.com/learn/clinmicronow.

Robert A. Britton, Micalis Institute, INRA, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, France.

Patrice D. Cani, Baylor College of Medicine, Molecular Virology and Microbiology, Houston, Texas.

Contributors vii

About the Editors xii

Preface xiii

A. Traditional Probiotic Approaches

1 Biochemical Features of Beneficial Microbes: Foundations for Therapeutic Microbiology 3
Melinda A. Engevik and James Versalovic

2 The Genomic Basis of Lactobacilli as Health-Promoting Organisms 49
Elisa Salvetti and Paul W. OToole

3 Bifidobacteria and Their Health-Promoting Effects 73
Claudio Hidalgo-Cantabrana, Susana Delgado, Lorena Ruiz, Patricia Ruas-Madiedo, Borja Sánchez, and Abelardo Margolles

B. Next-Generation Bacteriotherapy: Opportunities in Chronic Diseases

4 Microbial Interactions and Interventions in Colorectal Cancer 101
Terence Van Raay and Emma Allen-Vercoe

5 Microbial Impact on Host Metabolism: Opportunities for Novel Treatments of Nutritional Disorders? 131
Hubert Plovier and Patrice D. Cani

6 Therapeutic Opportunities in the Vaginal Microbiome 149
Gregor Reid

7 Lung Microbiota and Its Impact on the Mucosal Immune Phenotype 161
Benjamin G. Wu and Leopoldo N. Segal

8 Microbiota, Liver Diseases, and Alcohol 187
Anne-Marie Cassard, Philippe Gérard, and Gabriel Perlemuter

9 The Potential of Probiotics as a Therapy for Osteoporosis 213
Fraser L. Collins, Naiomy D. Rios-Arce, Jonathan D. Schepper, Narayanan Parameswaran, and Laura R. McCabe

10 Ecological Therapeutic Opportunities for Oral Diseases 235
Anilei Hoare, Philip D. Marsh, and Patricia I. Diaz

C. Control of Infectious Disease by Microbes

11 Control of Clostridium difficile Infection by Defined Microbial Communities 269
James Collins and Jennifer M. Auchtung

12 Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile 291
Guido J. Bakker and Max Nieuwdorp

13 Enterococci and Their Interactions with the Intestinal Microbiome 309
Krista Dubin and Eric G. Pamer

D. Next-Generation Microbial Therapeutics: Tools and Regulation

14 Engineering Diagnostic and Therapeutic Gut Bacteria 333
Brian P. Landry and Jeffrey J. Tabor

15 Use of Traditional and Genetically Modified Probiotics in Human Health: What Does the Future Hold? 363
Luis G. Bermúdez-Humarán and Philippe Langella

16 Genetic Tools for the Enhancement of Probiotic Properties 371
Laura Ortiz-Velez and Robert Britton

17 Genome Editing of Food-Grade Lactobacilli to Develop Therapeutic Probiotics 389
Jan-Peter van Pijkeren and Rodolphe Barrangou

18 United States Regulatory Considerations for Development of Live Biotherapeutic Products as Drugs 409
Sheila M. Dreher-Resnick, Scott Stibitz, and Paul E. Carlson, Jr.

E. Indirect Strategies to Target Microbiome Function for Health

19 Bacteriophage Clinical Use as Antibacterial Drugs: Utility and Precedent 419
Stephen T. Abedon

20 Modulation of the Gastrointestinal Microbiome with Nondigestible Fermentable Carbohydrates to Improve Human Health 453
Edward C. Deehan, Rebbeca M. Duar, Anissa M. Armet, Maria Elisa Perez-Muñoz, Mingliang Jin, and Jens Walter

Index 485