Table Of Content642_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
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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
