The Normal Bacterial Flora of Humans (page 3)
(This chapter has 5 pages)
© Kenneth Todar, PhD
The
Composition of the Normal Flora
The normal flora of humans are exceedingly complex and consist
of
more
than 200 species of bacteria. The makeup of the normal flora may be
influenced by various factors, including genetics, age, sex, stress,
nutrition
and
diet of the individual.
Three developmental changes in humans, weaning,
the eruption of the teeth, and the onset and cessation
of ovarian functions, invariably affect the composition of the normal
flora
in the intestinal tract, the oral cavity, and the vagina, respectively.
However, within the limits of these fluctuations, the bacterial flora
of
humans is sufficiently constant to a give general description of the
situation.
A human first becomes colonized by a normal flora at the moment of
birth and passage through the birth canal. In utero, the fetus
is sterile, but when the mother's water breaks and the birth process
begins, so does colonization of the body surfaces. Handling and
feeding of the infant after birth leads to establishment of a
stable normal flora on the skin, oral cavity and intestinal tract in
about 48
hours.
It has been calculated that a human adult houses about 1012
bacteria on the skin, 1010 in the mouth, and 1014
in the gastrointestinal tract. The latter number is far in excess of
the
number of eucaryotic cells in all the tissues and organs which comprise
a human.
The predominant bacteria on the surfaces of the
human body are listed in Table 3. Informal names identify the bacteria
in this table.
Formal taxonomic names of organisms are given in Table 1.
Table
3.
Predominant bacteria at various anatomical locations in adults.
Anatomical
Location
|
Predominant
bacteria
|
Skin
|
staphylococci
and corynebacteria
|
Conjunctiva
|
sparse,
Gram-positive cocci and
Gram-negative rods
|
Oral cavity
|
|
teeth |
streptococci,
lactobacilli |
mucous membranes
|
streptococci and
lactic
acid bacteria
|
Upper
respiratory tract
|
|
nares (nasal membranes) |
staphylococci
and corynebacteria |
pharynx (throat)
|
streptococci,
neisseria,
Gram-negative rods and cocci
|
Lower
respiratory tract
|
none
|
Gastrointestinal
tract
|
|
stomach
|
Helicobacter
pylori (up to 50%)
|
small intestine
|
lactics,
enterics, enterococci,
bifidobacteria
|
colon
|
bacteroides,
lactics, enterics,
enterococci, clostridia, methanogens
|
Urogenital tract
|
|
anterior urethra
|
sparse,
staphylococci,
corynebacteria,
enterics
|
vagina
|
lactic acid
bacteria during
child-bearing years; otherwise mixed
|
Normal Flora of the Skin The
adult
human is covered with approximately 2 square meters of skin. The
density
and composition of the normal flora of the skin varies with anatomical
locale.
The high moisture content of the axilla, groin, and areas between the
toes
supports the activity and growth of relatively high densities of
bacterial
cells, but the density of bacterial populations at most other sites is
fairly low, generally in 100s or 1000s per square cm. Most bacteria on
the skin are sequestered in sweat glands.
The skin microbes found in the most
superficial
layers of the epidermis and the upper parts of the hair follicles are
Gram-positive cocci (Staphylococcus epidermidis and Micrococcus
sp.) and corynebacteria such as Propionibacterium
sp. These are generally nonpathogenic and
considered
to be commensal, although mutualistic and parasitic roles have been
assigned
to them. For example, staphylococci and propionibacteria produce fatty
acids that inhibit the growth of fungi and yeast on the
skin. But, if
Propionibacterium acnes, a
normal inhabitant of the skin, becomes
trapped in hair follicle, it may grow rapidly and cause inflammation
and
acne.
Sometimes potentially pathogenic Staphylococcus aureus is
found on the face and hands in individuals who are nasal
carriers. This is because the face and hands are likely to become
inoculated with the bacteria on the nasal membranes. Such individuals
may autoinoculate themselves with the pathogen or spread it to other
individuals or foods.
Normal Flora of the
Conjunctiva
A variety of bacteria may be cultivated from the normal conjunctiva,
but
the number of organisms is usually small. Staphylococcus epidermidis
and certain coryneforms (Propionibacterium
acnes) are dominant. Staphylococcus
aureus, some streptococci, Haemophilus sp. and Neisseria
sp. are occasionally found. The conjunctiva is kept moist and healthy
by
the continuous secretions from the lachrymal glands. Blinking wipes the
conjunctiva every few seconds mechanically washing away foreign objects
including bacteria. Lachrymal secretions (tears) also contain
bactericidal
substances including lysozyme. There is little or no opportunity for
microorganisms
to colonize the conjunctiva without special mechanisms to attach to the
epithelial surfaces and some ability to withstand attack by lysozyme.
Pathogens
which do infect the conjunctiva (e.g. Neisseria gonorrhoeae and
Chlamydia
trachomatis) are thought to be able to specifically attach to the
conjunctival
epithelium. Newborn infants may be especially prone to bacterial
attachment. Since Chlamydia
and Neisseria might be
present on the cervical and vaginal epithelium of an infected mother,
silver nitrate or an antibiotic may be put into the newborn's eyes to
avoid infection after passage through the birth canal.
Figure
4. Colonies
of Propionibacterium
acnes,
found on skin and the conjunctiva.
Normal Flora of the Respiratory
Tract
A large number of bacterial species colonize the upper respiratory
tract
(nasopharynx). The nares (nostrils) are always heavily colonized,
predominantly with Staphylococcus
epidermidis and corynebacteria, and often (in about 20% of the
general
population) with Staphylococcus aureus, this being the main
carrier
site of this important pathogen. The healthy sinuses, in contrast are
sterile. The pharynx (throat) is normally colonized by
streptococci and various Gram-negative cocci. Sometimes pathogens such
as Streptococcus
pneumoniae, Streptococcus pyogenes, Haemophilus influenzae and Neisseria
meningitidis colonize the pharynx.
The lower respiratory tract
(trachea,
bronchi,
and pulmonary tissues) is virtually free of microorganisms,
mainly because of the efficient cleansing action of the ciliated
epithelium
which lines the tract. Any bacteria reaching the lower respiratory
tract
are swept upward by the action of the mucociliary blanket that lines
the
bronchi, to be removed subsequently by coughing, sneezing, swallowing,
etc. If the respiratory tract epithelium becomes damaged, as in
bronchitis
or viral pneumonia, the individual may become susceptible to infection
by pathogens such as H. influenzae or
S.
pneumoniae descending from the nasopharynx.
Normal Flora of the Urogenital
Tract
Urine is normally sterile, and since the urinary tract is flushed with
urine every few hours, microorganisms have problems gaining access and
becoming established. The flora of the anterior urethra, as indicated
principally
by urine cultures, suggests that the area my be inhabited by a
relatively
consistent normal flora consisting of Staphylococcus epidermidis,
Enterococcus
faecalis and some alpha-hemolytic streptococci. Their numbers are
not
plentiful, however. In addition, some enteric bacteria (e.g. E.
coli, Proteus)
and corynebacteria, which are probably contaminants from the skin,
vulva
or rectum, may occasionally be found at the anterior urethra.
The vagina becomes colonized soon after birth with corynebacteria,
staphylococci, streptococci, E. coli, and a lactic acid
bacterium
historically
named "Doderlein's bacillus" (Lactobacillus acidophilus). During
reproductive life, from puberty to menopause, the vaginal epithelium
contains
glycogen due to the actions of circulating estrogens. Doderlein's
bacillus
predominates, being able to metabolize the glycogen to lactic acid. The
lactic acid and other products of metabolism inhibit colonization by
all
except this lactobacillus and a select number of lactic acid
bacteria.
The resulting low pH of the vaginal epithelium prevents establishment
by
most other bacteria as well as the potentially-pathogenic yeast, Candida
albicans.
This
is a striking example of the protective effect of the normal bacterial
flora for their human host.
Figure
5. A Lactobacillus species,
possibly
Doderlein's bacillus, in association
with a vaginal epithelial cell.
Normal Flora of the Oral
Cavity
The presence of nutrients, epithelial debris, and secretions makes the
mouth a favorable habitat for a great variety of bacteria. Oral
bacteria
include streptococci, lactobacilli, staphylococci and corynebacteria,
with
a great number of anaerobes, especially bacteroides.
The mouth presents a succession of different ecological situations
with
age, and this corresponds with changes in the composition of the normal
flora. At birth, the oral cavity is composed solely of the soft tissues
of the lips, cheeks, tongue and palate, which are kept moist by the
secretions
of the salivary glands. At birth the oral cavity is sterile but rapidly
becomes colonized from the environment, particularly from the mother in
the first feeding. Streptococcus salivarius is dominant and
may
make up 98% of the total oral flora until the appearance of the teeth
(6
- 9 months in humans). The eruption of the teeth during the first year
leads to colonization by S. mutans and S. sanguis.
These
bacteria require a nondesquamating (nonepithelial) surface in order to
colonize. They will persist as long as teeth remain. Other strains of
streptococci
adhere strongly to the gums and cheeks but not to the teeth. The
creation
of the gingival crevice area (supporting structures of the teeth)
increases
the habitat for the variety of anaerobic species found. The complexity
of the oral flora continues to increase with time, and bacteroides and
spirochetes colonize around puberty.
Figure
6. Various
streptococci in a biofilm in the oral cavity.
The normal bacterial flora of the oral cavity clearly benefit from
their host who provides nutrients and habitat. There may be
benefits, as well, to the
host. The normal flora occupy available colonization sites which
makes
it more difficult for other microorganisms (nonindigenous species) to
become
established. Also, the oral flora contribute to host nutrition through
the synthesis of vitamins, and they contribute to immunity by inducing
low levels of circulating and secretory antibodies that may cross react
with pathogens. Finally, the oral bacteria exert microbial antagonism
against
nonindigenous species by production of inhibitory substances such as
fatty acids,
peroxides and bacteriocins.
On the other hand, the oral flora are the usual cause of various
oral diseases
in humans, including abscesses, dental caries, gingivitis, and
periodontal disease. If oral bacteria can gain entrance into
deeper tissues, they may cause abscesses of alveolar bone, lung,
brain, or the extremities. Such infections usually contain mixtures of
bacteria
with Bacteroides melaninogenicus often playing a dominant role.
If oral streptococci are introduced into wounds created by dental
manipulation or treatment,
they may adhere to heart valves and
initiate
subacute bacterial endocarditis.
Figure
7. Colonies
of E. coli growing on EMB agar.
Normal
Flora of the
Gastrointestinal Tract
The bacterial flora of the gastrointestinal (GI) tract of animals
has been studied more
extensively than that of any other site. The composition differs
between
various animal species, and within an animal species. In humans, there
are differences in the composition of the flora which are influenced by
age, diet, cultural conditions, and the use of antibiotics. The
latter
greatly perturbs the composition of the intestinal flora.
In the upper GI tract of adult humans, the esophagus contains only
the
bacteria swallowed with saliva and food. Because of the high acidity of
the gastric juice, very few bacteria (mainly acid-tolerant
lactobacilli)
can be cultured from the normal stomach. However, at least half
the
population in the United States is colonized by a pathogenic bacterium,
Helicobacter
pylori. Since the 1980s, this bacterium has been known to be
the cause of gastric ulcers, and it is probably a cause of gastric and
duodenal cancer as well. The Australian microbiologist, Barry Marshall,
received the Nobel Prize in Physiology and Medicine in 2005, for
demonstrating the relationship between Helicobacter and gastric
ulcers.
Figure
8. Helicobacter
pylori. ASM
The proximal small intestine has a relatively sparse Gram-positive
flora,
consisting mainly of lactobacilli and Enterococcus faecalis.
This region has about 105 - 107 bacteria per ml
of
fluid. The distal part of the small intestine contains greater numbers
of bacteria (108/ml) and additional species, including
coliforms (E. coli and
relatives)
and Bacteroides, in addition to lactobacilli and enterococci.
The
flora of the large intestine (colon) is qualitatively similar to that
found
in feces. Populations of bacteria in the colon reach levels of 1011/ml
feces. Coliforms become more prominent, and enterococci, clostridia and
lactobacilli can be regularly found, but the predominant species are
anaerobic
Bacteroides
and anaerobic lactic acid bacteria in the genus Bifidobacterium
(Bifidobacterium bifidum). These organisms may outnumber E.
coli
by 1,000:1 to 10,000:1. Sometimes, significant numbers of
anaerobic
methanogens (up to 1010/gm) may reside in the
colon
of humans. This is our only direct association with archaea as normal
flora. The range of incidence of certain bacteria in the large
intestine
of humans is shown in Table 4 below.
Table 4. Bacteria found in the
large intestine
of humans.
BACTERIUM |
RANGE OF INCIDENCE |
Bacteroides
fragilis |
100 |
Bacteroides
melaninogenicus |
100 |
Bacteroides
oralis |
100 |
Lactobacillus |
20-60 |
Clostridium
perfringens |
25-35 |
Clostridium
septicum |
5-25 |
Clostridium
tetani |
1-35 |
Bifidobacterium
bifidum |
30-70 |
Staphylococcus
aureus |
30-50 |
Enterococcus
faecalis |
100 |
Escherichia
coli |
100 |
Salmonella
enteritidis |
3-7 |
Klebsiella
sp. |
40-80 |
Enterobacter
sp. |
40-80 |
Proteus
mirabilis |
5-55 |
Pseudomonas
aeruginosa |
3-11 |
Peptostreptococcus
sp. |
?common |
Peptococcus
sp. |
?common
|
At birth the entire intestinal tract is sterile, but bacteria enter
with the first feed. The initial colonizing bacteria vary with the food
source of the infant. In breast-fed infants, bifidobacteria account for
more than 90% of the total intestinal bacteria. Enterobacteriaceae
and enterococci are regularly present, but in low proportions, while
bacteroides,
staphylococci, lactobacilli and clostridia are practically absent. In
bottle-fed
infants, bifidobacteria are not predominant. When breast-fed infants
are
switched to a diet of cow's milk or solid food, bifidobacteria are
progressively
joined by enterics, bacteroides, enterococci lactobacilli and
clostridia.
Apparently, human milk contains a growth factor that enriches for
growth
of bifidobacteria, and these bacteria play an important role in
preventing
colonization of the infant intestinal tract by non indigenous or
pathogenic
species.
Figure
9. Clostridium
difficile. Gram stain. The growth of "C. diff" in the intestinal
tract is normally held in check by other members of the normal flora.
When antibiotics given for other infections cause collateral damage to
the normal intestinal flora, the clostridium may be able to "grow out"
and produce a serious diarrheal syndrome called pseudomembranous
colitis. This is an example of an "antibiotic induced diarrheal disease".
The composition of the flora of the gastrointestinal tract varies
along
the tract (at longitudinal levels) and across the tract (at horizontal
levels) where certain bacteria attach to the gastrointestinal
epithelium
and others occur in the lumen. There is frequently a very close
association
between specific bacteria in the intestinal ecosystem and specific gut
tissues or cells (evidence of tissue tropism and specific adherence).
Gram-positive bacteria, such as the streptococci and lactobacilli, are
thought to adhere to the gastrointestinal epithelium using
polysaccharide
capsules or cell wall teichoic acids to attach to specific receptors on
the epithelial cells. Gram-negative bacteria such as the
enterics
may attach by means of specific fimbriae which
bind
to glycoproteins on the epithelial cell surface.
It is in the intestinal tract that we see the greatest effect of the
bacterial flora on their host. This is due to their large mass and
numbers. Bacteria in the human GI tract have been shown to produce
vitamins and may otherwise contribute
to nutrition and digestion. But their most important effects are in
their ability to protect their host from establishment and
infection by
alien microbes and their ability to stimulate the development and the
activity of the immunological tissues.
On the other hand, some of the bacteria in the colon (e.g. Bacteroides) have been shown to
produce metabolites that are carcinogenic, and there may be an
increased incidence of colon cancer associated with these bacteria.
Alterations in the GI flora brought on by poor nutrition or perturbance
with antibiotics can cause shifts in populations and colonization by
nonresidents that leads to gastrointestinal disease.