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642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page i Gut Ecology 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page iii Gut Ecology Ailsa L Hart BMBChMRCP Department of Gastroenterology, StMark’s Hospital, London, UK Andrew J Stagg PhD Antigen Presentation Research Group, Faculty of Medicine, Imperial College at Northwick Park Hospital, London, UK Hans Graffner MDPhD Associate Professor and Medical Director, Gastrointestinal Therapy Area, AstraZeneca R & D Mölndal, Mölndal, Sweden Hans Glise MDPhD Associate Professor, Department of Surgery, Linköpings University Hospital, and Head of Gastrointestinal Therapy Area, AstraZeneca R & D Mölndal, Mölndal, Sweden Per Falk MDPhD Associate Professor and Head of Molecular Biology, AstraZeneca R & D Mölndal, Mölndal, Sweden Michael A Kamm MDFRACPFRCP Professor of Gastroenterology and Chairman of Medicine, St Mark’s Hospital, London, UK MARTIN DUNITZ CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2002 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Version Date: 20130401 International Standard Book Number-13: 978-1-4822-0755-2 (eBook - PDF) This book contains information obtained from authentic and highly regarded sources. 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Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page v Contents Contributors vii Preface xi Part 1: The normal flora and techniques of identification 1 1 The normal flora of the gastrointestinal tract 3 2 The gut microflora: traditional and molecular identification techniques 13 3 The gut microflora: functional identification techniques 19 4 The ‘unculturables’ 25 Summary and observations 34 Part 2: The host response to the normal intestinal flora 37 5 Immune regulation of the normal intestinal bacterial flora 39 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page vi vi Contents 6 Modification of host cell function by normal flora – a molecular perspective 51 7 Bacteria and the regulation of T-cell immune function in the gut 57 Summary and observations 66 Part 3: Food, prebiotics and bacteria 71 8 Coeliac disease: a model to study oral tolerance 73 9 Effects of prebiotics on human gut health 81 Summary and observations 89 Part 4: Intestinal bacteria and mechanisms of disease 91 10 Genetically determined mucosal immune responses to normal resident luminal bacteria 93 11 Defensins and antimicrobial peptides 101 12 Defending against enteric infections 109 Summary and observations 121 Part 5: Modification of the intestinal flora 123 13 Modification of gut microflora: a novel treatment target in childhood disease 125 14 Inflammatory bowel disease: rationale for therapeutic focus on gut flora 135 15 Inflammatory bowel disease and probiotics 147 Summary and observations 156 Index 161 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page vii Contributors S Peter Borriello Kevin Collins Director Associate Professor Central Public Health Laboratory Department of Microbiology &Medicine 61 Colindale Ave University College London NW9 5HT, UK Cork, Ireland [email protected] [email protected] Jonathan Braun Per Falk Professor and Chair Associate Professor & Department of Pathology and Laboratory Head of Molecular Biology Medicine AstraZeneca R & D Mölndal UCLA School of Medicine CHS 13–222 S-431 83 Mölndal, Sweden Los Angeles, CA 90095–1732, USA [email protected] [email protected] Göte Forsberg Massimo Campieri Departments of Clinical Sciences, Pediatrics, Professor of Medicine & and Clinical Microbiology, Immunology Head of Inflammatory Bowel Disease Unit Umeå University Department of Internal Medicine and S-901 85 Umeå, Sweden Gastroenterology [email protected] Policlinico Sant’Orsola-Malpighi Via Massarenti, 9 40138 Bologna, Italy [email protected] 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page viii viii Contributors Glenn R Gibson Marie-Louise Hammarström Professor of Food Microbiology Department of Clinical Microbiology, Food Microbial Sciences Unit Immunology Science and Technology Centre Umeå University University of Reading S-901 85 Umeå, Sweden Whiteknights [email protected] PO Box 226 Reading RG6 6AP, UK Sten Hammarström [email protected] Department of Clinical Microbiology, Immunology Paolo Gionchetti Umeå University IBDUnit S-901 85 Umeå, Sweden Department of Internal Medicine and [email protected] Gastroenterology Policlinico Sant’Orsola-Malpighi Ailsa L Hart Via Massarenti 9 Department of Gastroenterology 40138 Bologna, Italy St Mark’s Hospital [email protected] Watford Road Harrow HA1 3UJ, UK Hans Glise [email protected] Head of Gastrointestinal Therapy Area AstraZeneca R & D Mölndal Olle Hernell S-431 83 Mölndal, Sweden Professor of Paediatrics [email protected] Department of Clinical Sciences, Paediatrics Umeå University Hans Graffner S-901 85 Umeå, Sweden Associate Professor and Medical Director [email protected] Gastroenterology Therapy Area AstraZeneca R & D Mölndal Erika Isolauri S-431 83 Mölndal, Sweden Professor of Paediatrics [email protected] Department of Paediatrics University of Turku 20520 Turku, Finland erika.isolauri@utu.fi 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page ix Contributors ix Anneli Ivarsson Thomas T MacDonald Departments of Clinical Sciences, Pediatrics, Professor of Immunology and Public Health and Clinical Medicine, Director of the Division of Infection, Allergy, Epidemiology Inflammation and Repair Umeå University Mailpoint 813 S-901 85 Umeå, Sweden Level E, South Block [email protected] University of Southampton School of Medicine Southampton SO16 6YD, UK Martin F Kagnoff [email protected] Director Laboratory of Mucosal Immunology University of California, San Diego Andrew J Macpherson 9500 Gilman Drive (MTF/412) Institute of Experimental Immunology La Jolla, CA 92093–0623, USA Universitätsspital [email protected] Schmelzbergstrasse 12 CH8091 Zürich, Switzerland Michael A Kamm [email protected] Professor of Gastroenterology and Chairman of Medicine Tore Midtvedt St Mark’s Hospital Laboratory of Medical Microbial Ecology Watford Road Karolinska Institute Harrow HA1 3UJ, UK Box 285 [email protected] S-171 77 Stockholm, Sweden [email protected] Alain Lamarre Institute of Experimental Immunology Liam O’Mahony Universitätsspital Senior Research Scientist Schmelzbergstrasse 12 National Food Biotechnology Centre CH8091 Zürich, Switzerland University College [email protected] Cork, Ireland [email protected] 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page x x Contributors Giovanni Monteleone Fergus Shanahan Research Fellow Department of Medicine Division of Infection, Inflammation and Repair, University College Mailpoint 813 Cork, Ireland Level E, South Block [email protected] University of Southampton School of Medicine Southampton SO16 6YD, UK Andrew J Stagg [email protected] Antigen Presentation Research Group Imperial College School of Medicine Fernando Rizzello Northwick Park Institute of Medical Research IBD Unit Watford Road Department of Internal Medicine and Harrow HA1 3UJ, UK Gastroenterology [email protected] Policlinico Sant’Orsola-Malpighi Via Massarenti, 9 Gerald W Tannock 40138 Bologna, Italy Professor of Microbiology [email protected] Department of Microbiology University of Otago Seppo Salminen PO Box 56 Professor 700 Cumberland Street Department of Biochemistry and Food Dunedin, New Zealand Chemistry [email protected] University of Turku 20014 Turku, Finland Therese Uhr sepsal@utu.fi Institute of ExperimentalImmunology Universitätsspital R Balfour Sartor Schmelzbergstrasse 12 Professor of Medicine, Microbiology and CH8091 Zürich, Switzerland Immunology [email protected] Department of Medicine/Division of Digestive Diseases CB#7038 Room 032A Glaxo Building Chapel Hill, NC 27599–7038, USA [email protected] 642_GUT ECOLOGY.prelims 17/12/2001 10 23 am Page xi Preface Lifelong cross-talk occurs between the host and the intestinal flora, and the outcome of this can determine whether health is maintained or disease intervenes. Our knowledge of the intestinal flora in health is limited. However, a combination of sophisticated molecular techniques, in conjunction with traditional microbiological methods, will pave the way for a greater understanding of this complex organ. This knowledge can then be used to explore disease prevention and treatment. An understanding of the bacteria-to-bacteria and bacteria-to- immune-cell interactions in the gastrointestinal tract will provide us with possible mechanisms of disease pathogenesis and potential ways of modulating the gastrointestinal microenvironment. In particular, under certain circumstances, the intestinal flora appears to have a role in driving inflammation. It remains to be seen which components of the flora are important in this process. Indeed, it may be that unique bacterial antigens are associated with disease in hosts with different genetic backgrounds. Manipulating such a complex ecosystem is challenging. Therapeutic interventions are superimposed on a complex background with a high signal-to-noise ratio. Nonetheless, there is tantalising evidence from animal and human studies
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