Advances in Experimental Medicine and Biology, Volume 635: GI Microbiota and Regulation of the Immune System

**Gary B. Huffnagle**, PhD, is a Professor of Internal Medicine (Pulmonary Diseases) and Microbiology and Immunology at the University of Michigan Medical School. He holds a BS in microbiology from Pennsylvania State University and a PhD in immunology from the University of Texas Southwestern Medical School. In addition to conducting research, he teaches undergraduate and graduate classes in eukaryotic microbiology, microbial symbiosis and experimental immunology at the University of Michigan. Dr. Huffnagle’s research focuses on the regulation of pulmonary immunity to infectious agents and allergens. In the past 5 years, his attention has turned to the role of the indigenous microbiota in immune system functioning, as well as the role of probiotics in animal and human health. He has been awarded research grants from the National Heart, Lung and Blood Institute (NHL BI), National Institute of Allergy and Infectious Diseases (NIAID), the Francis Families Foundation and the Burroughs-Wellcome Fund. Dr. Huffnagle serves or has served on editorial boards for the American Society for Microbiology (ASM) and the American Association of Immunologists (AAI), as well as on advisory and review panels for the National Institutes of Health (NIH). **Mairi C. Nove rr**, PhD, is an Assistant Professor of Immunology and Microbiology at Wayne State University Medical School. She earned a BA in biology from Kalamazoo College in 1996 and a PhD in microbiology and immunology from the University of Michigan in 2002. Dr. Noverr’s current research focuses on investigating mechanisms of immunomodulation by the opportunistic yeast Candida albicans during host-pathogen interactions and how interactions with other members of the microbiota influence these interactions. Her laboratory is investigating signaling compounds called oxylipins that are produced by both Candida and the host, which can influence the microbiology of the fungus and the activity of host immune system cells. Projects in the laboratory include molecular characterization of the fungal oxylipin biosynthetic pathways and determining the effects of oxylipins during Candida pathogenesis, in modulating host immune cell function, and during fungal-bacterial interactions. She has been awarded research funding from the Francis Families Foundation. The idea that the microbial communities within the GI tract have a profound influence on general human health actually originated with Russian scientist Elie Metchnikov at the turn of the last century. Also known as the a oefather of immunologya, Metchnikov believed that putrefactive bacteria in the gut were responsible for enhancing the aging process. He theorized that ingestion of healthy bacteria found in fermented foods could counteract toxic bacteria and was the key to good health. His theories concerning good bacteria and health can be found in his treatise a oeThe Prolongation of Life: Optimistic Studiesa . These writings prompted Japanese scientist Minoru Shirota to begin investigation of how fermentative bacteria improve health. He succeeded in isolating a strain of Lactobacillus that could survive passage through the intestine, while promoting a healthy balance of microbes. The a oeShirota straina is still used today in the fermented beverage Yakult. It is clear from a commercial standpoint that these ideas have inspired the development of a probiotic industry, which has expanded greatly in the U.S. over the past 5-10 years. Likewise, scientific studies investigating the microbiota and the immune system have increased significantly in recent years. This increase in research is also due to advances in technologies that enable the investigation of large microbial communities, a resurgence in gnotobiotic animal research, and improved methods for molecular analysis of probiotic bacterial species. Our interest in this area stems from our laboratory observations indicating that antibiotics and fungi can skew microbiota composition and systemic immune responses. Our initial baseof references upon which to develop further hypotheses concerning the mechanisms involved in microbiota regulation of immune responses was limited. However, in presenting the research at national scientific meetings and at universities across the country, the feedback and interest were overwhelming. It became clear that a book dedicated to current trends in investigating the GI microbiota was warranted. Dissection of the relationship between the microbiota and the immune system is currently being approached from a variety of angles that we have sought to incorporate into this book. This book opens with two general reference chapters, which provide an overview of current knowledge of gastrointestinal immunology and the commensal microbiology of the gut. Next are two chapters dedicated to current methodologies used to investigate the microbiota and host: molecular analysis of microbial diversity and gnotobiotic research. Both positive and negative interactions between the microbiota and the immune system can take place in the gut, with chapters dedicated to probiotics and intestinal diseases associated with unhealthy microbiota. Environmental factors play an enormous role in shaping the microbiota composition. Host, microbial, and dietary factors take part in a complex interplay, which provides many distinct and diverse research subjects. We have included a chapter discussing diet, functional foods, and prebiotics, which are dietary supplements used to specifically enhance the growth of beneficial members of the microbiota. Several laboratories are investigating how the different members of the microbiota communicate with each other and with the immune system. A chapter reviewing howbacteria sense and respond to signaling compounds in the gut environment provides insight into the signal transduction pathways that mediate interactions between the host and microbiota. A highly detailed and well-investigated model of bacterial-host symbiosis provides an immense amount of background and insight for the developing field of host-microbiota studies. We have included a chapter reviewing the unique interactions that take place in a non-mammalian system, the Squid-Vibrio model. Finally, we close the book with two chapters outlining current hypotheses concerned with redefining our understanding of the relationship between microbes, disease, and the basic mechanisms of immune system function.

The idea that the microbial communities within the GI tract have a profound influence on general human health actually originated with Russian scientist Elie Metchnikov at the turn of the last century. Also known as the “father of immunology”, Metchnikov believed that putrefactive bacteria in the gut were responsible for enhancing the aging process. He theorized that ingestion of healthy bacteria found in fermented foods could counteract toxic bacteria and was the key to good health. His theories concerning good bacteria and health can be found in his treatise “The Prolongation of Life: Optimistic Studies”. These writings prompted Japanese scientist Minoru Shirota to begin investigation of how fermentative bacteria improve health. He succeeded in isolating a strain of Lactobacillus that could survive passage through the intestine, while promoting a healthy balance of microbes. The “Shirota strain” is still used today in the fermented beverage Yakult. It is clear from a commercial standpoint that these ideas have inspired the development of a probiotic industry, which has expanded greatly in the U.S. over the past 5-10 years. Likewise, scientific studies investigating the microbiota and the immune system have increased significantly in recent years. This increase in research is also due to advances in technologies that enable the investigation of large microbial communities, a resurgence in gnotobiotic animal research, and improved methods for molecular analysis of probiotic bacterial species. Our interest in this area stems from our laboratory observations indicating that antibiotics and fungi can skew microbiota composition and systemic immune responses. Our initial base of references upon which to develop further hypotheses concerning the mechanisms involved in microbiota regulation of immune responses was limited. However, in presenting the research at national scientific meetings and at universities across the country, the feedback and interest were overwhelming. It became clear that a book dedicated to current trends in investigating the GI microbiota was warranted. Dissection of the relationship between the microbiota and the immune system is currently being approached from a variety of angles that we have sought to incorporate into this book. This book opens with two general reference chapters, which provide an overview of current knowledge of gastrointestinal immunology and the commensal microbiology of the gut. Next are two chapters dedicated to current methodologies used to investigate the microbiota and host: molecular analysis of microbial diversity and gnotobiotic research. Both positive and negative interactions between the microbiota and the immune system can take place in the gut, with chapters dedicated to probiotics and intestinal diseases associated with unhealthy microbiota. Environmental factors play an enormous role in shaping the microbiota composition. Host, microbial, and dietary factors take part in a complex interplay, which provides many distinct and diverse research subjects. We have included a chapter discussing diet, functional foods, and prebiotics, which are dietary supplements used to specifically enhance the growth of beneficial members of the microbiota. Several laboratories are investigating how the different members of the microbiota communicate with each other and with the immune system. A chapter reviewing how bacteria sense and respond to signaling compounds in the gut environment provides insight into the signal transduction pathways that mediate interactions between the host and microbiota. A highly detailed and well-investigated model of bacterial-host symbiosis provides an immense amount of background and insight for the developing field of host-microbiota studies. We have included a chapter reviewing the unique interactions that take place in a non-mammalian system, the Squid-Vibrio model. Finally, we close the book with two chapters outlining current hypotheses concerned with redefining our understanding of the relationship between microbes, disease, and the basic mechanisms of immune system function.

The Idea That The Microbial Communities Within The Gi Tract Have A Profound Influence On General Human Health Actually Originated With Russian Scientist Elie Metchnikov At The Turn Of The Last Century. These Writings Prompted Japanese Scientist Minoru Shirota To Begin Investigation Of How Fermentative Bacteria Improve Health. He Succeeded In Isolating A Strain Of Lactobacillus That Could Survive Passage Through The Intestine, While Promoting A Healthy Balance Of Microbes. The Shirota Strain Is Still Used Today In The Fermented Beverage Yakult. This Book Opens With Two General Reference Chapters, Which Provide An Overview Of Current Knowledge Of Gastrointestinal Immunology And The Commensal Microbiology Of The Gut. Next Are Two Chapters Dedicated To Current Methodologies Used To Investigate The Microbiota And Host: Molecular Analysis Of Microbial Diversity And Gnotobiotic Research. Both Positive And Negative Interactions Between The Microbiota And The Immune System Can Take. Overview Of Gut Immunology / Katie Lynn Mason ... [et Al.] -- The Commensal Microbiology Of The Gastrointestinal Tract / Janet M. Manson, Marcus Rauch And Michael S. Gilmore -- Overview Of The Gastrointestinal Microbiota / -- Vincent B. Young And Thomas M. Schmidt -- Effects Of Microbiota On Gi Health : Gnotobiotic Research / Robert Doug Wagner -- Positive Interactions With The Microbiota : Probiotics / Marko Kalliomäki, Seppo Salminen And Erika Isolauri -- Negative Interactions With The Microbiota : Ibd / Nita H. Salzman And Charles L. Bevins -- Diet, Immunity And Functional Foods / Lesley Hoyles And Jelena Vulevic -- Host-microbe Communication Within The Gi Tract / Christopher A. Allen And Alfredo G. Torres -- Host-microbe Symbiosis : The Squid-vibrio Association : A Naturally Occurring, Experimental Model Of Animal/bacterial Partnerships / Margaret Mcfall-ngai -- The Microflora Hypothesis Of Allergic Disease / Andrew Shreiner, Gary B. Huffnagle And Mairi C. Noverr -- The Damage-response Framework Of Microbial Pathogenesis And Infectious Diseases / Liise-anne Pirofski And Arturo Casadevall. Edited By Gary B. Huffnagle, Mairi C. Noverr. Includes Bibliographical References And Index. Overview of gut immunology / Katie Lynn Mason ... [et al.] The commensal microbiology of the gastrointestinal tract / Janet M. Manson, Marcus Rauch and Michael S. Gilmore Overview of the gastrointestinal microbiota / Vincent B. Young and Thomas M. Schmidt Effects of microbiota on GI health : Gnotobiotic research / Robert Doug Wagner Positive interactions with the microbiota : probiotics / Marko Kalliomøki, Seppo Salminen and Erika Isolauri Negative interactions with the microbiota : IBD / Nita H. Salzman and Charles L. Bevins Diet, immunity, and functional foods / Lesley Hoyles and Jelena Vulevic Host : microbe communication within the GI tract / Christopher A. Allen and Alfredo G. Torres Host : microbe symbiosis : the squid, vibrio association : a naturally occurring, experimental model of animal/bacterial partnerships / Margaret McFall-Ngai The "microflora hypothesis" of allergic disease / Andrew Shreiner, Gary B. Huffnagle and Mairi C. Noverr The damage : response framework of microbial pathogenesis and infectious diseases / Liise-anne Pirofski and Arturo Casadevall. Front Matter....Pages i-xvi Overview of Gut Immunology....Pages 1-14 The Commensal Microbiology of the Gastrointestinal Tract....Pages 15-28 Overview of the Gastrointestinal Microbiota....Pages 29-40 Effects of Microbiota on GI Health: Gnotobiotic Research....Pages 41-56 Positive Interactions with the Microbiota: Probiotics....Pages 57-66 Negative Interactions with the Microbiota: IBD....Pages 67-78 Diet, Immunity and Functional Foods....Pages 79-92 Host-Microbe Communication within the GI Tract....Pages 93-101 Host-Microbe Symbiosis: The Squid-Vibrio Association—A Naturally Occurring, Experimental Model of Animal/Bacterial Partnerships....Pages 102-112 The “Microflora Hypothesis” of Allergic Disease....Pages 113-134 The Damage-Response Framework of Microbial Pathogenesis and Infectious Diseases....Pages 135-146 Back Matter....Pages 147-149 Offers an overview of the knowledge of gastrointestinal immunology and the commensal microbiology of the gut. This book includes chapters dedicated to methodologies used to investigate the microbiota and host: molecular analysis of microbial diversity and gnotobiotic research