Preface

The human gastrointestinal tract microorganisms, termed the "microbiota," have been investigated since the beginning of microbiological studies, when Antonie van Leeuwenhoek, the father of microbiology, investigated the microorganisms in his own stools. The human microbiota comprises trillions of microbes distributed in various niches throughout the intestinal tract and is one of the most complex microbial ecosystems on earth. The host and its microbiota have co-evolved together, and considering the staggering numbers and diversity, it is therefore not surprising that the microbiota exert a major influence on the host. The original term for the microbiota upon discovery was the "flora" or "microflora," literally translated as "small plants," which has a botanical connotation. These terms are still used widely today and internationally recognized. Nevertheless, it is considered more appropriate to use the term microbiota, i.e., "small life" taking into account that the human microbiota is comprised of bacteria, archaea, bacteriophage, a smaller number of yeasts, and some protozoa; hence, this term is mainly used throughout this book. With this book, we have made an attempt to cover all issues associated with the gastrointestinal microbiota, from health to disease and from sampling to identification. Although various books have addressed the intestinal microbiota, this has mainly been from the perspective of disease or nutrition, while the microbiota itself has rarely been the focus. This current book aims to fill this gap and provide the reader with a comprehensive overview of all aspects related to the gastrointestinal microbiota. There have been major scientific advances especially in human intestinal microbiology in the recent past, which are also covered by the contributions.

Early studies were limited to description of the culturable microbes, which as we now realize, made up only a minority of the gastrointestinal tract microbiota. Due to the development of molecular biological techniques over the last decade, microbes can now be detected and studied to a large extent, without the need for culturing. In the first chapter, Kaouther Ben Amor and Elaine Vaughan review the major achievements of recent times in determining the diversity of the microbiota using modern molecular techniques, based on 16S ribosomal RNA, as well as methods to evaluate their activity within the various niches. Research of the gastrointestinal tract microbiota, especially in the case of humans, is often restricted to fecal material. In fact, a range of other sampling techniques are available, which are presented by Angele Kerckhoffs and colleagues, to access the small intestine, as well as noninvasive sampling methods that are routinely used in medical practice. This is an important issue since feces represent only the luminal material of the terminal colon and will provide insufficient information about other locations of the gut. Anne McCartney and Glenn Gibson describe the succession of the microbiota in infants, as well as the earlier culturing studies, and the methodology to characterize the microbiota down to subspecies level. It has long been recognized that the intestinal microbiota plays an important role in maintaining health in infants. Currently, much attention is also focused on the intestinal microbiota of the elderly, as is discussed in the chapter by Fang He. In western nations, the elderly are becoming a more numerous segment of the population, and it is becoming increasingly established that intestinal health has a major role in their quality of life.

While establishing the microbiota diversity and their activity (live versus dead) is a major challenge, it is essential to know and understand their effects on the host. The intestinal microbiota has a major influence on the development and maintenance of our immune system as described by Marie-Christiane Moreau. Because of their direct contact with the host, the activity and interaction of the microbiota with the intestinal mucosa may be more important than the activity of microbes in the lumen, as described by Wai Ling Chow and Yuan-Kun Lee. The human microbiota also play a major role in our nutrition. Barry Goldin reviews the myriad of metabolic possibilities of the human microbiota concerning the metabolism of food ingredients and drugs we consume, as well as host-derived substrates. Max Bingham focuses on the metabolism by the microbiota of polyphenols, which are considered to be key active constituents of fruits and vegetables and responsible for many of the health protective effects of diets rich in these foods. Today, functional genomics technologies are developing and will facilitate our ability to detect the microbes and determine the molecular mechanisms of their impact on the host. Through the sequencing of an ever-increasing number of microbiota genomes, and elegant molecular studies, a further understanding is being obtained into the molecular functioning of the host-microbiota interactions, a dynamic area that is discussed by Peter Bron, Willem de Vos, and Michiel Kleerebezem.

The gastrointestinal tract microbiota is receiving more attention than ever in particular in relation to disease. Fergus Shanahan, Barbara Sheil, and coworkers review the relationship between the intestinal microbiota and inflammatory bowel diseases, as well as give an overview of the probiotic clinical trials and the potential mechanisms of probiotics for ameliorating these intestinal diseases. Through its metabolism, the intestinal microbiota is thought to play an important role in both the etiology and prevention of colorectal cancer, as discussed by Patricia Heavey, Ian Rowland, and Joseph Rafter. In addition to diseases of the gastrointestinal tract, Pirkka Kirjavainen and Gregor Reid also discuss that diseases such as allergy are being recognized to have an "intestinal component," again mediated through the interaction between the microbiota and the intestinal immune system.

In order to gain a better understanding of the composition and functioning of the intestinal microbiota and how this can be influenced, intestinal models have been developed; this allows for a simplification of the complex intestinal ecosystem as presented by Harri Makivuokko and Paivi Nurminen. Experimental animals, as described by Anders Henriksson, have also been highly valuable for this purpose, especially with the availability of various knockout animal models for disease. Also the use of animals with a "human" microbiota provide valuable models to investigate the influence of substances on the microbiota and host physiology. The best animal models to show the importance of the intestinal microbiota are germ-free animals. Their physiological differences compared to conventional animals are striking and show clearer than any other model the role intestinal microbes play, as discussed by Elisabeth Norin and Tore Midtvedt. Because of its influence on the health and well being of the host, strategies have been devised to alter the composition and/or activity of the intestinal microbiota. Antibiotics have long been known to alter the composition of the intestinal microbiota, as discussed by Asa Sullivan and Carl Erik Nord, which may lead to various side effects, depending on the activity spectrum of the antibiotic. Methods to improve the activity and composition of the intestinal microbiota include probiotics, microbes ingested orally that provide beneficial effects, and prebiotics substrates that are selectively metabolized by the beneficial native gastrointestinal tract microbes, as discussed in the chapters by Chandraprakash Khedkar and Arthur Ouwehand, and Ross Crittenden and Martin Playne, respectively.

The major part of the book deals with the microbiota of humans, and when animals are studied, it is often as a model for humans. Minna Rinkinen describes the microbiota of companion animals, an area that has received very little attention to date, although the well being of pets can contribute significantly to the well being of the owner. In the case of farm animals, discussed by Alojz Bomba and colleagues, there is an important economic drive where the role of the microbiota on performance is a major focus. This will only become more important from 2006 onward as antimicrobial growth promoters will be prohibited in the European Union.

Gastrointestinal Microbiology is a vibrant field of research that is benefiting from many interdisciplinary interactions between different research groups in the world, that are using, developing, and applying novel technologies. Exciting initiatives are emerging with high through put technologies such as sequence analysis of the human microbiome (collective genomes of the gut microbiota) and metabolomics applied to microbiota and nutritional research. There is occasionally some overlap in information scattered throughout the book that is valuable since the reader will get an appreciation for the different opinions and perspectives that reflect the current state of research findings in the literature for this subject. It remains a highly complex task to understand the mutual relationship between members of the microbial community in the gut and their interaction with the host.

Finally, we hope that all readers will share our excitement for this dynamic subject that impacts on all our lives.

Arthur C. Ouwehand Elaine E. Vaughan

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