Table Of ContentBacteriology of Humans
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For the Wilson clan – Andrew, Anne, Caroline, Edie, Fionn, Joan, Liz, Pippa, and Sarah
– a rare example of a complex community governed only by positive interactions.
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Bacteriology of
Humans
An Ecological Perspective
Michael Wilson
University College London
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© 2008 by Blackwell Publishing Ltd
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1
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CONTENTS
Preface, ix
Abbreviations of genera, xi
1 THE HUMAN–MICROBE SYMBIOSIS, 1
1.1 Overview of the nature and distribution of
the microbial communities inhabiting
humans, 1
1.1.1 Difficulties encountered in determining
the composition of a microbial
community, 2
1.1.2 Structural aspects of microbial
communities, 5
1.1.2.1 Microcolonies, 5
1.1.2.2 Intracellular colonization, 5
1.1.2.3 Biofilms, 6
1.1.3 Communication in microbial
communities, 8
1.2 Environmental determinants that affect the
distribution and composition of microbial
communities, 13
1.2.1 Nutritional determinants, 14
1.2.2 Physicochemical determinants, 18
1.2.3 Mechanical determinants, 22
1.2.4 Biological determinants, 23
1.3 Host characteristics that affect the indigenous
microbiota, 27
1.3.1 Age, 28
1.3.2 Host genotype, 29
1.3.3 Gender, 29
1.4 Techniques used to characterize the microbial
communities inhabiting humans, 31
1.4.1 Microscopy, 31
1.4.2 Culture-dependent approaches, 33
1.4.3 Culture-independent, molecular
approaches, 35
1.4.4 Functional analysis of microbial
communities, 37
1.5 The epithelium – site of host–microbe
interactions, 37
1.5.1 Structure of epithelia, 38
1.5.2 The epithelium as an excluder of
microbes, 41
1.5.3 Mucus and mucins, 41
1.5.4 Innate and acquired immune responses at
the mucosal surface, 46
1.6 Further reading, 53
1.6.1 Books, 53
1.6.2 Reviews and papers, 53
2 THE INDIGENOUS MICROBIOTA OF
THE SKIN, 56
2.1 Anatomy and physiology of human skin, 56
2.2 Cutaneous antimicrobial defense systems, 56
2.2.1 Innate defense systems, 58
2.2.2 Acquired immune defense systems, 60
2.3 Environmental determinants operating at
different skin regions, 61
2.4 The indigenous microbiota of the skin, 67
2.4.1 Members of the cutaneous microbiota, 67
2.4.1.1 Corynebacterium spp., 67
2.4.1.2 Propionibacterium spp., 70
2.4.1.3 Staphylococcus spp., 71
2.4.1.4 Micrococcus spp., 73
2.4.1.5 Malassezia spp., 75
2.4.1.6 Acinetobacter spp., 76
2.4.1.7 Brevibacterium spp., 78
2.4.1.8 Dermabacter hominis, 79
2.4.1.9 Methylobacterium spp., 79
2.4.2 Community composition at different sites,
80
2.4.3 Culture-independent studies of the
cutaneous microbiota, 86
2.4.4 Interactions among members of the
cutaneous microbiota, 88
2.5 Overview of the cutaneous microbiota, 90
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vi
Contents
2.6 Sources of data used to compile figures , 92
2.7 Further reading, 92
2.7.1 Books, 92
2.7.2 Reviews and papers, 92
3 THE INDIGENOUS MICROBIOTA OF
THE EYE, 95
3.1 Anatomy and physiology of the eye, 95
3.2 Antimicrobial defense systems of the eye, 97
3.3 Environmental determinants on the conjunctival
surface, 99
3.4 The indigenous microbiota of the eye, 103
3.4.1 Members of the ocular microbiota, 103
3.4.2 Composition of the ocular microbiota, 104
3.4.3 Interactions among members of the ocular
microbiota, 107
3.5 Overview of the ocular microbiota, 111
3.6 Sources of data used to compile figures, 111
3.7 Further reading, 111
4 THE INDIGENOUS MICROBIOTA OF
THE RESPIRATORY TRACT, 113
4.1 Anatomy and physiology of the respiratory
tract, 113
4.1.1 Nose, 113
4.1.2 Pharynx, 114
4.1.3 Larynx, 114
4.1.4 Trachea, 114
4.1.5 Bronchi and bronchioles, 114
4.1.6 Alveolus, 115
4.2 Antimicrobial defense systems of the respiratory
tract, 117
4.2.1 Nasal cavity, 117
4.2.2 Other regions of the conducting
portion, 119
4.2.3 Respiratory portion, 119
4.3 Environmental determinants within the
respiratory tract, 119
4.3.1 Atmospheric composition, 119
4.3.2 pH, 120
4.3.3 Nutrients, 120
4.3.3.1 Composition of nasal fluid, ASL,
and alveolar lining fluid, 120
4.3.3.2 Contribution of microbial
residents of the respiratory tract to
nutrient availability, 122
4.4 Indigenous microbiota of the respiratory
tract, 123
4.4.1 Members of the respiratory microbiota,
123
4.4.1.1 Streptococcus spp., 123
4.4.1.1.1 Strep. pyogenes, 124
4.4.1.1.2 Strep. pneumoniae, 126
4.4.1.1.3 Viridans group
streptococci, 128
4.4.1.2 Neisseria spp., 128
4.4.1.2.1 N. meningitidis, 129
4.4.1.2.2 Other Neisseria spp.,
131
4.4.1.3 Haemophilus spp., 131
4.4.1.3.1 H. influenzae, 132
4.4.1.3.2 Other Haemophilus spp.,
134
4.4.1.4 Moraxella catarrhalis, 135
4.4.1.5 Staphylococci, 136
4.4.1.5.1 Staph. aureus, 136
4.4.1.5.2 CNS, 138
4.4.1.6 Mollicutes, 139
4.4.1.7 Kingella kingae, 140
4.4.2 Community composition at the various
sites within the respiratory tract, 140
4.4.2.1 Nasal vestibule, 142
4.4.2.2 Nasal cavity, 143
4.4.2.3 Nasopharynx, 146
4.4.2.4 Oropharynx, 146
4.4.2.5 Lower respiratory tract, 151
4.4.3 Interactions among members of the
respiratory microbiota, 152
4.5 Overview of the respiratory microbiota, 152
4.6 Sources of data used to compile figures, 155
4.7 Further reading, 157
5 THE INDIGENOUS MICROBIOTA
OF THE URINARY SYSTEM OF
FEMALES, 159
5.1 Anatomy and physiology of the urinary system of
females, 159
5.2 Antimicrobial defenses of the female urinary
system, 160
5.3 Environmental determinants within the female
urethra, 161
5.4 The indigenous microbiota of the female urethra,
162
5.4.1 Members of the urethral microbiota, 163
5.4.2 Community composition in the female
urethra, 164
5.5 Overview of the microbiota of the urinary tract of
females, 167
5.6 Sources of data used to compile figures, 168
5.7 Further reading, 168
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6 THE INDIGENOUS MICROBIOTA OF
THE REPRODUCTIVE SYSTEM OF
FEMALES, 170
6.1 Anatomy and physiology of the female
reproductive system, 170
6.2 Antimicrobial defense systems of the female
reproductive system, 172
6.2.1 Innate defense systems, 173
6.2.2 Acquired immune defense systems, 174
6.3 Environmental determinants at different regions
of the reproductive system, 176
6.3.1 Vagina, 176
6.3.2 Cervix, 179
6.3.3 Vulva, 179
6.3.4 Contribution of the indigenous microbiota
to nutrient supply within the reproductive
system, 179
6.4 The indigenous microbiota of the female
reproductive system, 181
6.4.1 Members of the microbiota, 181
6.4.1.1 Lactobacillus spp., 181
6.4.1.2 Gardnerella vaginalis, 184
6.4.1.3 Candida albicans, 184
6.4.1.4 Streptococcus agalactiae (Group B
streptococcus), 186
6.4.1.5 Mycoplasma hominis, 186
6.4.1.6 Ureaplasma urealyticum, 186
6.4.1.7 Atopobium vaginae, 187
6.4.1.8 Mobiluncus spp., 187
6.4.2 Community composition at different sites
within the female reproductive system, 187
6.4.2.1 Vagina, 187
6.4.2.1.1 Post-menarcheal/pre-
menopausal females,
187
6.4.2.1.2 Pre-menarcheal girls,
191
6.4.2.1.3 Post-menopausal
women, 192
6.4.2.1.4 Vaginal microbiota
during pregnancy, 193
6.4.2.2 Cervix, 193
6.4.2.2.1 Post-menarcheal/pre-
menopausal females,
197
6.4.2.2.2 Cervical microbiota
during pregnancy, 197
6.4.2.3 Vulva, 199
6.4.3 Interactions between organisms colonizing
the female reproductive system, 200
6.5 Overview of the microbiota of the female
reproductive system, 202
6.6 Sources of data used to compile figures, 202
6.7 Further reading, 204
6.7.1 Books, 204
6.7.2 Reviews and papers, 204
7 THE INDIGENOUS MICROBIOTA OF
THE URINARY AND REPRODUCTIVE
SYSTEMS OF MALES, 207
7.1 Anatomy and physiology, 207
7.2 Antimicrobial defenses of the male urinary and
reproductive systems, 207
7.3 Environmental determinants within the male
urinary and reproductive systems, 210
7.4 The indigenous microbiota of the male urinary
and reproductive systems, 211
7.4.1 Members of the microbiota, 211
7.4.2 Microbiota of the male urethra, 212
7.4.3 Microbiota of the glans penis, 216
7.4.4 Microbiota of the prostate, 218
7.5 Overview of the microbiota of the male urinary
and reproductive systems, 218
7.6 Sources of data used to compile figures, 219
7.7 Further reading, 220
8 THE INDIGENOUS MICROBIOTA OF
THE ORAL CAVITY, 222
8.1 Anatomy and physiology of the oral cavity, 222
8.2 Antimicrobial defense systems of the oral cavity,
225
8.3 Environmental determinants at the various sites
within the oral cavity, 228
8.3.1 Mechanical determinants, 228
8.3.2 Nutritional determinants, 228
8.3.3 Physicochemical determinants, 231
8.4 The indigenous microbiota of the oral cavity, 232
8.4.1 Members of the oral microbiota, 235
8.4.1.1 Oral streptococci and related
Gram-positive cocci, 235
8.4.1.2 Gemella spp., 235
8.4.1.3 Actinomyces spp., 236
8.4.1.4 Rothia dentocariosa, 237
8.4.1.5 Veillonella spp., 237
8.4.1.6 Anaerobic and microaerophilic
Gram-negative rods, 237
8.4.1.6.1 Fusobacterium spp., 237
8.4.1.6.2 Porphyromonas spp.,
238
8.4.1.6.3 Prevotella spp., 239
Contents
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Contents
8.4.1.6.4 Spirochaetes, 239
8.4.1.6.5 Other anaerobic
species, 239
8.4.1.7 Facultatively anaerobic Gram-
negative bacilli, 240
8.4.1.8 Mycoplasma spp., 240
8.4.1.9 Megasphaera spp., 241
8.4.2 Community composition at different
sites, 241
8.4.2.1 Supragingival plaque, 241
8.4.2.2 Gingival crevice, 253
8.4.2.3 Tongue, 256
8.4.2.4 Other mucosal surfaces, 257
8.5 Overview of the oral microbiota, 261
8.6 Sources of data used to compile figures, 263
8.7 Further reading, 264
8.7.1 Books, 264
8.7.2 Reviews and papers, 264
9 THE INDIGENOUS MICROBIOTA OF
THE GASTROINTESTINAL TRACT, 266
9.1 Anatomy and physiology of the gastrointestinal
tract, 267
9.2 Antimicrobial defense systems of the
gastrointestinal tract, 272
9.2.1 Innate defense systems, 272
9.2.2 Acquired immune defense system, 275
9.3 Environmental determinants within different
regions of the gastrointestinal tract, 276
9.3.1 Esophagus, 276
9.3.2 Stomach, 277
9.3.3 Small intestine, 277
9.3.4 Large intestine, 278
9.4 The indigenous microbiota of the gastrointestinal
tract, 280
9.4.1 Members of the intestinal microbiota, 282
9.4.1.1
Bacteroides, 282
9.4.1.2
Eubacterium, 283
9.4.1.3
Roseburia, 284
9.4.1.4
Clostridium, 284
9.4.1.5
Bifidobacterium, 284
9.4.1.6
Enterococcus, 285
9.4.1.7
Helicobacter pylori, 286
9.4.1.8
Enterobacteriaceae, 286
9.4.1.9
Ruminococcus, 287
9.4.1.10 Methanogenic organisms, 287
9.4.1.11 Desulfovibrio, 287
9.4.1.12 Acidaminococcus, 288
9.4.1.13 Faecalibacterium prausnitzii, 288
9.4.2 Community composition in different
regions of the intestinal tract, 288
9.4.2.1 Esophagus, 288
9.4.2.2 Stomach, 289
9.4.2.3 Small intestine, 295
9.4.2.3.1 Duodenum, 295
9.4.2.3.2 Jejunum, 295
9.4.2.3.3 Ileum, 301
9.4.2.4 Large intestine, 302
9.4.2.4.1 Cecum, 304
9.4.2.4.2 Colon, 306
9.4.2.4.3 Rectum, 316
9.4.3 Microbial interactions in the
gastrointestinal tract, 317
9.5 Overview of the indigenous microbiota of the
gastrointestinal tract, 320
9.6 Sources of data used to compile figures, 320
9.7 Further reading, 322
9.7.1 Books, 322
9.7.2 Reviews and papers, 322
10 THE FUTURE, 327
10.1 Further reading, 329
Index, 331
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PREFACE
More than 50 years ago, Dylan’s The Times they Are
A-Changing reverberated around the planet and, with
an unerring sense of timelessness, those words are as
appropriate now as they were then. Unsurprisingly
to me, and to many others, they are applicable to the
science of bacteriology as well as to so many other
aspects of our existence. Hence, for many years, the pri-
mary focus of the vast majority of bacteriologists study-
ing the bacterial inhabitants of humans has been those
species responsible for disease, e.g. Streptococcus pyo-
genes, Haemophilus influenzae, Neisseria meningitidis,
Staphylococcus aureus, etc. What is now a-changing is
that interest is shifting towards the vast majority of our
microbial partners that do not cause disease and,
indeed, are essential to our well being. The indigenous
microbiota of healthy humans is now the subject of
intense scrutiny, and its enormous diversity and the
crucial roles that it plays in the development, protec-
tion, and maintenance of Homo sapiens are slowly being
revealed. In this book, I have concentrated on the first
of these, and have described the nature of the microbial
communities that inhabit the various regions of the
healthy human body. I have also attempted to explain
their presence at a particular site in terms of the envi-
ronmental factors that operate there. This book, I hope,
will be useful to undergraduates and postgraduates on
courses in microbiology, medical microbiology, micro-
bial ecology, infectious diseases, immunology, human
biology, medicine, dentistry, nursing, health sciences,
biomedical sciences, and pharmacy and, indeed, to all
those who have an interest in the complex microbial
communities with which we have co-evolved.
I am not sure why books need a preface, and I cannot
recall ever having read one. Nevertheless, it does give
the author an opportunity for self-indulgence and I am,
therefore, going to amuse myself by interweaving two
important threads in my life – bacteriology and Dylan.
Any reader who is not a Dylan fan should read no
further and should turn immediately to the table of
contents, which details what this book is about, or else
flick through the book and take a look at some of the
great figures that researchers have kindly supplied.
In mapping out the indigenous microbiota of humans,
anyone whose life has been pervaded by Dylan’s lyrics
cannot fail to see parallels. Bob – how come you knew
all this bacteriology? Which of the large variety of possi-
ble primary, secondary, and subsequent colonizers
arriving at any site is certainly determined by A Simple
Twist of Fate? But when a lonely bacterium’s “gravity
fails” ( Just Like Tom Thumb’s Blues) and it’s deposited on
the vast acidic, dry surfaces of the forearm, leg, or hand,
does it cry out in desperation “oh my God am I here all
alone?” (Ballad of a Thin Man). But it’s unlikely to suffer
for very long as the number of bacteria managing to
survive there is minimized by “Shedding off one more
layer of skin” (Jokerman).
To me, the colon, with its immense numbers of
tightly packed microbes, is epitomized by that incred-
ible line from Leopard Skin Pill Box Hat – “it balances on
your head just like a mattress balances on a bottle of
wine”. How can so many microbes be fitted into such a
small space, and how can such a sentence be fitted into
the song without breaking its rhythm? Idiot Wind, with
its acidic, bile-ridden lyrics just has to be the duodenum
– one of the most acidic regions of the body and perme-
ated by bile salts. The chances of bacteria surviving
there are low, and the chances of love flourishing in
that relationship are zero. Who could fail to Pity the
Poor Immigrant bacteria in the urethra – repeatedly
flushed away by a regular dowsing of urine. For them,
there’s nothing but Trouble. Is there nowhere they can
get Shelter from the Storm? And spare a thought for those
poor bacteria trying to colonize the conjunctiva who
are washed away by “buckets of tears” (Buckets of Rain)
– they must have the feeling that they’re Going, going,
gone. And lastly, of course, don’t forget the microbial
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