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The term normal microbial ora denotes the popula-

tion of microorganisms that inhabit the skin and


mucous membranes of healthy normal persons. It is
doubtful whether a normal viral ora exists in humans.
The skin and mucous membranes always harbor a
variety of microorganisms that can be arranged into two
groups: (1) The resident ora consists of relatively xed
types of microorganisms regularly found in a given area
at a given age; if disturbed, it promptly reestablishes
itself. (2) The transient ora consists of nonpathogenic
or potentially pathogenic microorganisms that inhabit
the skin or mucous membranes for hours, days, or
weeks; it is derived from the environment, does not pro-
duce disease, and does not establish itself permanently
on the surface. Members of the transient ora are gener-
ally of little signicance so long as the normal resident
ora remains intact. However, if the resident ora is dis-
turbed, transient microorganisms may colonize, prolif-
erate, and produce disease.
Organisms frequently encountered in specimens
obtained from various areas of the human bodyand
considered normal oraare listed in Table 111. The
classication of anaerobic normal bacterial ora is dis-
cussed in Chapter 22.
ROLE OF THE RESIDENT FLORA
The microorganisms that are constantly present on
body surfaces are commensals. Their flourishing in a
given area depends upon physiologic factors of tempera-
ture, moisture, and the presence of certain nutrients and
inhibitory substances. Their presence is not essential to
life, because germ-free animals can be reared in the
complete absence of a normal microbial flora. Yet the
resident flora of certain areas plays a definite role in
maintaining health and normal function. Members of
the resident ora in the intestinal tract synthesize vita-
min K and aid in the absorption of nutrients. On
mucous membranes and skin, the resident flora may
prevent colonization by pathogens and possible disease
through bacterial interference. The mechanism of
bacterial interference is not clear. It may involve compe-
tition for receptors or binding sites on host cells, compe-
tition for nutrients, mutual inhibition by metabolic or
toxic products, mutual inhibition by antibiotic materi-
als or bacteriocins, or other mechanisms. Suppression of
the normal ora clearly creates a partial local void that
tends to be lled by organisms from the environment or
from other parts of the body. Such organisms behave as
opportunists and may become pathogens.
On the other hand, members of the normal flora
may themselves produce disease under certain circum-
stances. These organisms are adapted to the noninvasive
mode of life dened by the limitations of the environ-
ment. If forcefully removed from the restrictions of that
environment and introduced into the bloodstream or
tissues, these organisms may become pathogenic. For
example, streptococci of the viridans group are the most
common resident organisms of the upper respiratory
tract. If large numbers of them are introduced into the
bloodstream (eg, following tooth extraction or tonsillec-
tomy), they may settle on deformed or prosthetic heart
valves and produce infective endocarditis. Small num-
bers occur transiently in the bloodstream with minor
trauma (eg, dental scaling or vigorous brushing). Bac-
teroides species are the commonest resident bacteria of
the large intestine and are quite harmless in that loca-
tion. If introduced into the free peritoneal cavity or into
pelvic tissues along with other bacteria as a result of
trauma, they cause suppuration and bacteremia. There
are many other examples, but the important point is
that microbes of the normal resident ora are harmless
and may be beneficial in their normal location in the
host and in the absence of coincident abnormalities.
They may produce disease if introduced into foreign
locations in large numbers and if predisposing factors
are present.
NORMAL FLORA OF THE SKIN
Because of its constant exposure to and contact with the
environment, the skin is particularly apt to contain tran-
sient microorganisms. Nevertheless, there is a constant
and well-defined resident flora, modified in different
196
Normal Microbial Flora
of the Human Body
11
4010_1-16 2/11/04 9:27 AM Page 196
anatomic areas by secretions, habitual wearing of cloth-
ing, or proximity to mucous membranes (mouth, nose,
and perineal areas).
The predominant resident microorganisms of the
skin are aerobic and anaerobic diphtheroid bacilli (eg,
corynebacterium, propionibacterium); nonhemolytic
aerobic and anaerobic staphylococci (Staphylococcus epi-
dermidis, occasionally S aureus, and peptostreptococcus
species); gram-positive, aerobic, spore-forming bacilli
that are ubiquitous in air, water, and soil; alpha-
hemolytic streptococci (viridans streptococci) and ente-
rococci (enterococcus species); and gram-negative col-
iform bacilli and acinetobacter. Fungi and yeasts are
often present in skin folds; acid-fast, nonpathogenic
mycobacteria occur in areas rich in sebaceous secretions
(genitalia, external ear).
Among the factors that may be important in elimi-
nating nonresident microorganisms from the skin are
the low pH, the fatty acids in sebaceous secretions, and
the presence of lysozyme. Neither profuse sweating nor
washing and bathing can eliminate or signicantly mod-
ify the normal resident ora. The number of supercial
microorganisms may be diminished by vigorous daily
scrubbing with soap containing hexachlorophene or
other disinfectants, but the ora is rapidly replenished
from sebaceous and sweat glands even when contact
with other skin areas or with the environment is com-
pletely excluded. Placement of an occlusive dressing on
skin tends to result in a large increase in the total micro-
bial population and may also produce qualitative alter-
ations in the ora.
Anaerobes and aerobic bacteria often join to form
synergistic infections (gangrene, necrotizing fasciitis,
cellulitis) of skin and soft tissues. The bacteria are fre-
quently part of the normal microbial ora. It is usually
difficult to pinpoint one specific organism as being
responsible for the progressive lesion, since mixtures of
organisms are usually involved.
NORMAL FLORA OF THE MOUTH
&UPPER RESPIRATORY TRACT
The ora of the nose consists of prominent corynebacte-
ria, staphylococci (S epidermidis, S aureus), and strepto-
cocci.
The mucous membranes of the mouth and pharynx
are often sterile at birth but may be contaminated by
passage through the birth canal. Within 412 hours
after birth, viridans streptococci become established as
the most prominent members of the resident ora and
remain so for life. They probably originate in the respi-
ratory tracts of the mother and attendants. Early in life,
aerobic and anaerobic staphylococci, gram-negative
diplococci (neisseriae, Moraxella catarrhalis), diph-
theroids, and occasional lactobacilli are added. When
teeth begin to erupt, the anaerobic spirochetes, pre-
votella species (especially P melaninogenica), fusobac-
terium species, rothia species, and capnocytophaga
species (see below) establish themselves, along with
some anaerobic vibrios and lactobacilli. Actinomyces
species are normally present in tonsillar tissue and on
the gingivae in adults, and various protozoa may also be
present. Yeasts (candida species) occur in the mouth.
In the pharynx and trachea, a similar ora establishes
itself, whereas few bacteria are found in normal bronchi.
Small bronchi and alveoli are normally sterile. The pre-
dominant organisms in the upper respiratory tract, par-
Table 111. Normal bacterial ora.
Skin
Staphylococcus epidermidis
Staphylococcus aureus (in small numbers)
Micrococcus species
Nonpathogenic neisseria species
Alpha-hemolytic and nonhemolytic streptococci
Diphtheroids
Propionibacteriumspecies
Peptostreptococcus species
Small numbers of other organisms (candida species, acine-
tobacter species, etc)
Nasopharynx
Any amount of the following: diphtheroids, non-
pathogenic neisseria species, -hemolytic streptococci;
S epidermidis, nonhemolytic streptococci, anaerobes
(too many species to list; varying amounts of prevotella
species, anaerobic cocci, fusobacterium species, etc)
Lesser amounts of the following when accompanied by
organisms listed above: yeasts, haemophilus species,
pneumococci, S aureus, gram-negative rods, Neisseria
meningitidis
Gastrointestinal tract and rectum
Various Enterobacteriaceae except salmonella, shigella,
yersinia, vibrio, and campylobacter species
Non-dextrose-fermenting gram-negative rods
Enterococci
Alpha-hemolytic and nonhemolytic streptococci
Diphtheroids
S aureus in small numbers
Yeasts in small numbers
Anaerobes in large numbers (too many species to list)
Genitalia
Any amount of the following: corynebacterium species,
lactobacillus species, -hemolytic and nonhemolytic
streptococci, nonpathogenic neisseria species
The following when mixed and not predominant: entero-
cocci, Enterobacteriaceae and other gram-negative
rods, S epidermidis, Candida albicans, and other yeasts
Anaerobes (too many to list); the following may be impor-
tant when in pure growth or clearly predominant: pre-
votella, clostridium, and peptostreptococcus species
NORMAL MICROBIAL FLORA OF THE HUMAN BODY / 197
4010_1-16 2/11/04 9:27 AM Page 197
ticularly the pharynx, are nonhemolytic and alpha-
hemolytic streptococci and neisseriae. Staphylococci,
diphtheroids, haemophili, pneumococci, mycoplasmas,
and prevotellae are also encountered.
Infections of the mouth and respiratory tract are usu-
ally caused by mixed oronasal flora, including anaer-
obes. Periodontal infections, perioral abscesses, sinusitis,
and mastoiditis may involve predominantly Prevotella
melaninogenica, fusobacteria, and peptostreptococci.
Aspiration of saliva (containing up to 10
2
of these
organisms and aerobes) may result in necrotizing pneu-
monia, lung abscess, and empyema.
The Role of the Normal Mouth Flora
in Dental Caries
Caries is a disintegration of the teeth beginning at the
surface and progressing inward. First the surface enamel,
which is entirely noncellular, is demineralized. This has
been attributed to the effect of acid products of bacterial
fermentation. Subsequent decomposition of the dentin
and cement involves bacterial digestion of the protein
matrix.
An essential rst step in caries production appears to
be the formation of plaque on the hard, smooth enamel
surface. The plaque consists mainly of gelatinous
deposits of high-molecular-weight glucans in which
acid-producing bacteria adhere to the enamel. The car-
bohydrate polymers (glucans) are produced mainly by
streptococci (Streptococcus mutans, peptostreptococci),
perhaps in association with actinomycetes. There
appears to be a strong correlation between the presence
of S mutans and caries on specific enamel areas. The
essential second step in caries production appears to be
the formation of large amounts of acid (pH < 5.0) from
carbohydrates by streptococci and lactobacilli in the
plaque. High concentrations of acid demineralize the
adjoining enamel and initiate caries.
In experimental germ-free animals, cariogenic
streptococci can induce the formation of plaque and
caries. Adherence to smooth surfaces requires both the
synthesis of water-insoluble glucan polymers by glucosyl-
transferases and the participation of binding sites on the
surface of microbial cells. (Perhaps carbohydrate poly-
mers also aid the attachment of some streptococci to
endocardial surfaces.) Other members of the oral
microora, eg, veillonellae, may complex with glucosyl-
transferase of Streptococcus salivarius in saliva and then
synthesize water-insoluble carbohydrate polymers to
adhere to tooth surfaces. Adherence may be initiated by
salivary IgA antibody to S mutans. Certain diphtheroids
and streptococci that produce levans can induce specic
soft tissue damage and bone resorption typical of peri-
odontal disease. Proteolytic organisms, including actino-
mycetes and bacilli, play a role in the microbial action on
dentin that follows damage to the enamel. The develop-
ment of caries also depends on genetic, hormonal, nutri-
tional, and many other factors. Control of caries involves
physical removal of plaque, limitation of sucrose intake,
good nutrition with adequate protein intake, and reduc-
tion of acid production in the mouth by limitation of
available carbohydrates and frequent cleansing. The
application of uoride to teeth or its ingestion in water
results in enhancement of acid resistance of the enamel.
Control of periodontal disease requires removal of calcu-
lus (calcied deposit) and good mouth hygiene.
Periodontal pockets in the gingiva are particularly rich
sources of organisms, including anaerobes, that are rarely
encountered elsewhere. While they may participate in
periodontal disease and tissue destruction, attention is
drawn to them when they are implanted elsewhere, eg,
producing infective endocarditis or bacteremia in a gran-
ulopenic host. Examples are capnocytophaga species and
Rothia dentocariosa. Capnocytophaga species are
fusiform, gram-negative, gliding anaerobes; rothia species
are pleomorphic, aerobic, gram-positive rods. Both prob-
ably participate in the complex microbial ora of peri-
odontal disease with prominent bone destruction. In
granulopenic immunodecient patients, they can lead to
serious opportunistic lesions in other organs.
NORMAL FLORA OF THE INTESTINAL
TRACT
At birth the intestine is sterile, but organisms are soon
introduced with food. In breast-fed children, the intes-
tine contains large numbers of lactic acid streptococci
and lactobacilli. These aerobic and anaerobic, gram-
positive, nonmotile organisms (eg, bifidobacterium
species) produce acid from carbohydrates and tolerate
pH 5.0. In bottle-fed children, a more mixed ora exists
in the bowel, and lactobacilli are less prominent. As
food habits develop toward the adult pattern, the bowel
ora changes. Diet has a marked inuence on the rela-
tive composition of the intestinal and fecal ora. Bowels
of newborns in intensive care nurseries tend to be colo-
nized by Enterobacteriaceae, eg, klebsiella, citrobacter,
and enterobacter.
In the normal adult, the esophagus contains microor-
ganisms arriving with saliva and food. The stomachs
acidity keeps the number of microorganisms at a mini-
mum (10
3
10
5
/g of contents) unless obstruction at the
pylorus favors the proliferation of gram-positive cocci
and bacilli. The normal acid pH of the stomach
markedly protects against infection with some enteric
pathogens, eg, cholera. Administration of cimetidine for
peptic ulcer leads to a great increase in microbial ora of
the stomach, including many organisms usually preva-
lent in feces. As the pH of intestinal contents becomes
alkaline, the resident flora gradually increases. In the
198 / CHAPTER 11
4010_1-16 2/11/04 9:27 AM Page 198
adult duodenum, there are 10
3
10
6
bacteria per gram of
contents; in the jejunum and ileum, 10
5
10
8
bacteria
per gram; and in the cecum and transverse colon,
10
8
10
10
bacteria per gram. In the upper intestine, lac-
tobacilli and enterococci predominate, but in the lower
ileum and cecum, the ora is fecal. In the sigmoid colon
and rectum, there are about 10
11
bacteria per gram of
contents, constituting 1030% of the fecal mass. Anaer-
obes outnumber facultative organisms by 1000-fold. In
diarrhea, the bacterial content may diminish greatly,
whereas in intestinal stasis the count rises.
In the normal adult colon, 9699% of the resident
bacterial ora consists of anaerobes: bacteroides species,
especially B fragilis; fusobacterium species; anaerobic lac-
tobacilli, eg, bifidobacteria; clostridia (C perfringens,
10
3
10
5
/g); and anaerobic gram-positive cocci (pep-
tostreptococcus species). Only 14% are facultative aer-
obes (gram-negative coliform bacteria, enterococci, and
small numbers of protei, pseudomonads, lactobacilli,
candidae, and other organisms). More than 100 distinct
types of organisms occur regularly in normal fecal ora.
Minor trauma (eg, sigmoidoscopy, barium enema) may
induce transient bacteremia in about 10% of procedures.
Intestinal bacteria are important in synthesis of vita-
min K, conversion of bile pigments and bile acids,
absorption of nutrients and breakdown products, and
antagonism to microbial pathogens. The intestinal ora
produces ammonia and other breakdown products that
are absorbed and can contribute to hepatic coma.
Among aerobic coliform bacteria, only a few serotypes
persist in the colon for prolonged periods, and most
serotypes of Escherichia coli are present only over a
period of a few days.
Antimicrobial drugs taken orally can, in humans, tem-
porarily suppress the drug-susceptible components of the
fecal ora. This is commonly done by the preoperative
oral administration of insoluble drugs. For example,
neomycin plus erythromycin can in 12 days suppress
part of the bowel ora, especially aerobes. Metronidazole
accomplishes that for anaerobes. If lower bowel surgery is
performed when the counts are at their lowest, some pro-
tection against infection by accidental spill can be
achieved. However, soon thereafter the counts of fecal
ora rise again to normal or higher than normal levels,
principally of organisms selected out because of relative
resistance to the drugs employed. The drug-susceptible
microorganisms are replaced by drug-resistant ones, par-
ticularly staphylococci, enterobacters, enterococci, protei,
pseudomonads, Clostridium difcile, and yeasts.
The feeding of large quantities of Lactobacillus aci-
dophilus may result in the temporary establishment of
this organism in the gut and the concomitant partial
suppression of other gut microora.
The anaerobic ora of the colon, including B fragilis,
clostridia, and peptostreptococci, plays a main role in
abscess formation originating in perforation of the
bowel. Prevotella bivia and P disiens are important in
abscesses of the pelvis originating in the female genital
organs. Like B fragilis, these species are penicillin-resis-
tant; therefore, another agent should be used.
NORMAL FLORA OF THE URETHRA
The anterior urethra of both sexes contains small num-
bers of the same types of organisms found on the skin
and perineum. These organisms regularly appear in nor-
mal voided urine in numbers of 10
2
10
4
/mL.
NORMAL FLORA OF THE VAGINA
Soon after birth, aerobic lactobacilli appear in the
vagina and persist as long as the pH remains acid (sev-
eral weeks). When the pH becomes neutral (remaining
so until puberty), a mixed flora of cocci and bacilli is
present. At puberty, aerobic and anaerobic lactobacilli
reappear in large numbers and contribute to the mainte-
nance of acid pH through the production of acid from
carbohydrates, particularly glycogen. This appears to be
an important mechanism in preventing the establish-
ment of other, possibly harmful microorganisms in the
vagina. If lactobacilli are suppressed by the administra-
tion of antimicrobial drugs, yeasts or various bacteria
increase in numbers and cause irritation and inamma-
tion. After menopause, lactobacilli again diminish in
number and a mixed ora returns. The normal vaginal
ora includes group B streptococci in as many as 25%
of women of childbearing age. During the birth process,
a baby can acquire group B streptococci, which subse-
quently may cause neonatal sepsis and meningitis. The
normal vaginal ora often includes also alpha hemolytic
streptococci, anaerobic streptococci (peptostreptococci),
prevotella species, clostridia, Gardnerella vaginalis, Ure-
aplasma urealyticum, and sometimes listeria or mobilun-
cus species. The cervical mucus has antibacterial activity
and contains lysozyme. In some women, the vaginal
introitus contains a heavy flora resembling that of the
perineum and perianal area. This may be a predisposing
factor in recurrent urinary tract infections. Vaginal
organisms present at time of delivery may infect the
newborn (eg, group B streptococci).
NORMAL FLORA OF THE CONJUNCTIVA
The predominant organisms of the conjunctiva are
diphtheroids (Corynebacterium xerosis), S epidermidis,
and nonhemolytic streptococci. Neisseriae and gram-
negative bacilli resembling haemophili (moraxella
species) are also frequently present. The conjunctival
flora is normally held in check by the flow of tears,
which contain antibacterial lysozyme.
NORMAL MICROBIAL FLORA OF THE HUMAN BODY / 199
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REVIEW QUESTIONS
1. A 26-year-old woman visits her physician
because of an unusual vaginal discharge. On
examination the physician observes a thin,
homogeneous, white-gray discharge that
adheres to the vaginal wall. The pH of the dis-
charge is 5.5 (normal: < 4.3). On Gram stain,
many epithelial cells covered with gram-vari-
able rods are seen. Bacterial vaginosis is diag-
nosed. Which one of the following normal geni-
tal flora microorganisms is present in greatly
decreased numbers in bacterial vaginosis?
(A) Corynebacteriumspecies
(B) Staphylococcus epidermidis
(C) Prevotella species
(D) Candida albicans
(E) Lactobacillus species
2. Certain microorganisms are never considered to
be members of the normal ora. They are always
considered to be pathogens. Which one of the
following organisms ts into that category?
(A) Streptococcus pneumoniae
(B) Escherichia coli
(C) Mycobacterium tuberculosis
(D) Staphylococcus aureus
(E) Neisseria meningitidis
3. A 9-year-old girl develops fever and severe pain
on the right side of her throat. On examination,
redness and swelling in the right peritonsillar
area are seen. A peritonsillar abscess is diag-
nosed. The most likely organisms to be cultured
from this abscess are
(A) Staphylococcus aureus
(B) Streptococcus pneumoniae
(C) Corynebacterium species and Prevotella
melaninogenica
(D) Normal oral nasal ora
(E) Viridans streptococci and Candida albicans
4. A 70-year-old man with a history of diverticulosis
of the sigmoid colon experiences a sudden onset
of severe left lower quadrant abdominal pain.
Fever develops. The severe pain gradually sub-
sides and is replaced by a constant aching pain
and marked abdominal tenderness. A diagnosis of
probable ruptured diverticulum is made and the
patient is taken to the operating room. The diag-
nosis of ruptured diverticulum is conrmed and
an abscess next to the sigmoid colon is found. The
most likely bacteria to be found in the abscess are
(A) Mixed normal gastrointestinal ora
(B) Bacteroides fragilis alone
(C) Escherichia coli alone
(D) Clostridium perfringens alone
(E) Enterococcus species alone
5. Antimicrobial therapy can decrease the amount
of susceptible bowel flora and allow prolifera-
tion of relatively resistant colonic bacteria.
Which one of the following species can prolifer-
ate and produce a toxin that causes diarrhea?
(A) Enterococcus species
(B) Staphylococcus epidermidis
(C) Pseudomonas aeruginosa
(D) Clostridium difcile
(E) Bacteroides fragilis
6. Which one of the following microorganisms can
be part of the normal vaginal flora and cause
meningitis in newborns?
(A) Candida albicans
(B) Corynebacteriumspecies
(C) Staphylococcus epidermidis
(D) Ureaplasma urealyticum
(E) Group B streptococci
7. Most serotypes of Escherichia coli can be
expected to remain in the colon for what period
of time?
(A) A few days
(B) A few weeks
(C) 6 months
(D) 2 years
(E) A lifetime
8. Which one of the following microorganisms is
closely associated with dental caries?
(A) Candida albicans
(B) Streptococcus mutans
(C) Prevotella melaninogenica
(D) Neisseria subava
(E) Staphylococcus epidermidis
9. Anaerobic bacteria such as Bacteroides fragilis occur
in the sigmoid colon in a concentration of about
10
11
/g of stool. At what concentration do faculta-
tive organisms such as Escherichia coli occur?
(A) 10
11
/g
(B) 10
10
/g
(C) 10
9
/g
(D) 10
8
/g
(E) 10
7
/g
10. Streptococcus pneumoniae can be part of the
normal flora of 540% of people. At what
anatomic site can it be found?
(A) Conjunctiva
(B) Nasopharynx
(C) Colon
(D) Urethra
(E) Vagina
(continued)
200 / CHAPTER 11
4010_1-16 2/11/04 9:27 AM Page 200
Answers
1. E 6. E
2. C 7. A
3. D 8. D
4. A 9. B
5. D 10. D
REFERENCES
Hentges DJ: The anaerobic microflora of the human body. Clin
Infect Dis 1993;16(Suppl 4):S175.
Macowiak PA: The normal microbial flora. N Engl J Med
1982;307:83.
The pathogenesis of periodontal diseases. J Periodontol
1999;70:457.
Redondo-Lopez V, Cook RL, Sobel JD: Emerging role of lacto-
bacilli in the control and maintenance of the vaginal bacterial
microora. Rev Infect Dis 1984;6(Suppl 1):S62.
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