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6
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C H A P T E R
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Normal Flora
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CHAPTER CONTENTS

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Concept of Normal Flora Normal Flora of the Genitourinary Tract
The Human Microbiome Pearls
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Normal Flora of the Skin Self-Assessment Questions
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Normal Flora of the Respiratory Tract Practice Questions: USMLE & Course Examinations
Normal Flora of the Intestinal Tract
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CONCEPT OF NORMAL FLORA the normal flora, although they can be present in asymp-
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Normal flora is the term used to describe the various bac- tomatic individuals. The normal flora organisms are often
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teria and fungi that are permanent residents of certain referred to as commensals. Commensals are organisms
body sites, especially the skin, oropharynx, colon, and that derive benefit from another host but do not damage
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vagina (Tables 6–1 and 6–2). Viruses and parasites (protozoa that host. The term human microbiome is often used to
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and helminths), which are the other major groups of describe the normal flora (see later).
The members of the normal flora vary in both number
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microorganisms, are usually not considered members of
and kind from one site to another. Although the normal
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flora extensively populates many areas of the body, the
TABLE 6–1 Summary of the Members of Normal internal organs usually are sterile. Areas such as the central
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Flora and Their Anatomic Locations nervous system, blood, lower bronchi and alveoli, liver,
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Members of the Normal Flora1 Anatomic Location spleen, kidneys, and bladder are free of all but the occa-
sional transient organism.
Bacteroides species Colon, throat, vagina
There is a distinction between the presence of these
Candida albicans Mouth, colon, vagina
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organisms and the carrier state. In a sense, we all are carriers

Clostridium species Colon of microorganisms, but that is not the normal use of the term
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Corynebacterium species Nasopharynx, skin, vagina in the medical context. The term carrier implies that an indi-
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(diphtheroids) vidual harbors a potential pathogen and therefore can be a
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Enterococcus faecalis Colon source of infection of others. It is most frequently used in

reference to a person with an asymptomatic infection or to fre
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Escherichia coli and other coliforms Colon, vagina, outer urethra
someone who has recovered from a disease but continues to
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Gardnerella vaginalis Vagina

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carry the organism and may shed it for a long period.

Haemophilus species Nasopharynx There is also a distinction to be made between members
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Lactobacillus species Mouth, colon, vagina of the normal flora, which are the permanent residents, and
the colonization of the individual with a new organism. In
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Neisseria species Mouth, nasopharynx

Propionibacterium acnes Skin
a sense, we are all colonized by the normal flora organisms,
but the term colonization typically refers to the acquisition
Pseudomonas aeruginosa Colon, skin
of a new organism. After the new organism colonizes (i.e.,
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Staphylococcus aureus Nose, skin attaches and grows, usually on a mucosal membrane), it
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Staphylococcus epidermidis Skin, nose, mouth, vagina, may cause an infectious disease, or it may be eliminated by
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urethra our host defenses. Furthermore, the person colonized by a

new organism can transmit that organism to others (i.e., act
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Viridans streptococci Mouth, nasopharynx

1
In alphabetical order. as a reservoir of infection for others).
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CHAPTER 6 Normal Flora 27

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TABLE 6–2 Medically Important Members of the Normal Flora
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Location Important Organisms1 Less Important Organisms2

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Skin Staphylococcus epidermidis Staphylococcus aureus, Corynebacterium (diphtheroids), various streptococci,
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Pseudomonas aeruginosa, anaerobes (e.g., Propionibacterium), yeasts (e.g.,
Candida albicans)
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Nose S. aureus3 S. epidermidis, Corynebacterium (diphtheroids), various streptococci
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Mouth Viridans streptococci Various streptococci, Eikenella corrodens
Dental plaque Streptococcus mutans Prevotella intermedia, Porphyromonas gingivalis
Gingival crevices Various anaerobes (e.g.,
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Bacteroides, Fusobacterium,
streptococci, Actinomyces)
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Throat Viridans streptococci Various streptococci (including Streptococcus pyogenes and Streptococcus
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pneumoniae), Neisseria species, Haemophilus influenzae, S. epidermidis
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Colon Bacteroides fragilis, Escherichia coli Bifidobacterium, Eubacterium, Fusobacterium, Lactobacillus, various aerobic
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gram-negative rods, Enterococcus faecalis and other streptococci, Clostridium

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Vagina Lactobacillus, E. coli,3 group B Various streptococci, various gram-negative rods. B. fragilis, Corynebacterium
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streptococci3 (diphtheroids), C. albicans
Urethra S. epidermidis, Corynebacterium (diphtheroids), various streptococci, various
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gram-negative rods (e.g., E. coli)3
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Organisms that are medically significant or present in large numbers.
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Organisms that are less medically significant or present in smaller numbers.
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These organisms are not part of the normal flora in this location but are important colonizers.
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The members of the normal flora play a role both in the gastrointestinal tract. The majority of these microbes are
maintenance of health and in the causation of disease in bacteria, but yeasts and protozoa are also found in large
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three significant ways: numbers. Using sophisticated molecular techniques, many
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previously unknown bacteria have been identified. Routine
(1) They can cause disease, especially in immunocom-
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cultures on bacteriological media typically reveal only a
promised and debilitated individuals. Although these
small subset of the existing resident organisms.
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organisms are nonpathogens in their usual anatomic loca-
It is estimated that the adult human contains 1013 cells
tion, they can be pathogens in other parts of the body.
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whereas the number of microbes in the human microbiome
(2) They constitute a protective host defense mechanism.
is approximately 1014, that is, there are 10 times more
The nonpathogenic resident bacteria occupy attachment
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microbial cells than human cells. The largest and most
sites on the skin and mucosa that can interfere with coloniza-
complex microbial population resides in the colon. Within
tion by pathogenic bacteria. The ability of members of the
the colon, the two largest phyla of bacteria are the Fir-
normal flora to limit the growth of pathogens is called colo-
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micutes (64%) and the Bacteroidetes (23%). The Firmicutes

nization resistance. If the normal flora is suppressed, patho-
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are gram-positive rods and members of the genera Clos-
gens may grow and cause disease. For example, antibiotics
tridium and Faecalibacterium are prominent organisms.
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can reduce the normal colonic flora that allows Clostridium
The Bacteroidetes are gram-negative rods and the genera,
difficile, which is resistant to the antibiotics, to overgrow and
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cause pseudomembranous colitis.

Bacteroides and Prevotella are important members. Species
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of Proteobacteria (gram-negative rods such as Escherichia

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(3) They may serve a nutritional function. The intesti-
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and Salmonella) and Actinobacteria (gram-positive rods

nal bacteria produce several B vitamins and vitamin K.
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such as Actinomyces) make up a large percentage of the

Poorly nourished people who are treated with oral antibi-
remainder.
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otics can have vitamin deficiencies as a result of the reduc-

There is mounting evidence that the organisms in the
tion in the normal flora. However, since germ-free animals
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microbiome play an important role in several body func-

are well-nourished, the normal flora is not essential for
tions and diseases, such as weight control (obesity), inflam-
proper nutrition.
matory bowel disease, the immune response in general, and
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resistance to infectious disease.

The effect on obesity is revealed by studies involving the
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THE HUMAN MICROBIOME transfer of fecal bacteria between strains of inbred mice.
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The human microbiome is the term used to describe the For example, fecal bacteria from obese mice transplanted
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thousands of microbes (“microbiota”) located on the skin, into germ-free strains of nonobese mice resulted in the
on mucosal surfaces, and within the lumen of the nonobese mice becoming obese. It appears that the fecal
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28 PART I Basic Bacteriology

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bacteria metabolize more of the input food making more NORMAL FLORA OF THE
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calories available to the mice. In other experiments, fecal
RESPIRATORY TRACT

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transplants from identical (monozygotic) human twins,
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one obese and the other not obese, were transplanted into A wide spectrum of organisms colonize the nose, throat,
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germ-free mice. The mice that received the fecal transplant and mouth, but the lower bronchi and alveoli typically con-
from the obese twin gained significantly more weight than tain few, if any, organisms. The nose is colonized by a vari-
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the mice that received the fecal transplant from the non- ety of streptococcal and staphylococcal species, the most
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obese twin. significant of which is the pathogen S. aureus. Occasional
The intestinal microbiota also plays a role in certain outbreaks of disease due to this organism, particularly in
autoimmune diseases such as the inflammatory bowel dis- the newborn nursery, can be traced to nasal, skin, or peri-
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eases, Crohn’s disease and ulcerative colitis. In the stool of anal carriage by health care personnel.
patients with these diseases, bacteria of the Proteobacteria The throat contains a mixture of viridans streptococci,
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and Actinobacteria genera were found in much greater Neisseria species, and S. epidermidis (see Table 6–2). These
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numbers than Firmicutes and Bacteroidetes whereas in nonpathogens occupy attachment sites on the pharyngeal
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those who do not have those diseases the opposite was mucosa and inhibit the growth of the pathogens Streptococcus
found, namely, the Firmicutes and Bacteroidetes greatly pyogenes, Neisseria meningitidis, and S. aureus, respectively.
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outnumbered the Proteobacteria and Actinobacteria. In the mouth, viridans streptococci make up about half
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In addition, the gut microbiota influences the matura- of the bacteria. Streptococcus mutans, a member of the viri-
tion and function of the immune response. Germ-free mice dans group, is of special interest since it is found in large
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do not produce lymphoid follicles in the small intestine, do numbers (1010/g) in dental plaque, the precursor of caries.
not produce secretory IgA, and do not produce CD8 The plaque on the enamel surface is composed of gelati-
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intraepithelial lymphocytes. Further, the presence of cer- nous, high-molecular-weight glucans secreted by the bacte-
tain members of the microbiota influences the proportion ria. The entrapped bacteria produce a large amount of acid,
of Th1, Th2, and Th17 T cells. which demineralizes the enamel and initiates caries. The
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Colonization resistance is another function of the viridans streptococci, such as S. sanguinis, are also the lead-
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microbiota. Within the colon, members of the intestinal ing cause of subacute bacterial (infective) endocarditis.
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flora prevent the overgrowth of Clostridium difficile, the These organisms can enter the bloodstream at the time of
cause of pseudomembranous colitis. When antibiotics kill dental surgery and attach to damaged heart valves.
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members of the colonic flora, colonization resistance is lost, Eikenella corrodens, also part of the normal oral flora,
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C. difficile overgrows, and colitis results. In some patients causes skin and soft tissue infections associated with
with intractable colitis, fecal transplants from unaffected human bites and “clenched-fist” injuries (i.e., injuries to the
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individuals cures the colitis. hand that occur during fist fights).
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Anaerobic bacteria, such as species of Bacteroides, Pre-
votella, Fusobacterium, Clostridium, and Peptostreptococcus,
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NORMAL FLORA OF THE SKIN are found in the gingival crevices, where the oxygen concen-
tration is very low. If aspirated, these organisms can cause
The predominant organism is Staphylococcus epidermidis, lung abscesses, especially in debilitated patients with poor
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which is a nonpathogen on the skin but can cause disease dental hygiene. In addition, the gingival crevices are the natu-
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when it reaches certain sites, such as artificial heart valves ral habitat of Actinomyces israelii—an anaerobic actinomycete
and prosthetic joints. It is found on the skin much more that can cause abscesses of the jaw, lungs, or abdomen.
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frequently than its pathogenic relative Staphylococcus
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aureus (see Table 6–2). There are about 103–104 organisms/ NORMAL FLORA OF THE fre
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cm2 of skin. Most of them are located superficially in the

INTESTINAL TRACT
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stratum corneum, but some are found in the hair follicles

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and act as a reservoir to replenish the superficial flora after In normal fasting people, the stomach contains few organ-
hand washing. Anaerobic organisms, such as Propionibac- isms, primarily because of its low pH. The small intestine
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terium and Peptococcus, are situated in the deeper follicles usually contains small numbers of streptococci, lactobacilli,
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in the dermis, where oxygen tension is low. Propionibacte- and yeasts, particularly C. albicans. Larger numbers of
rium acnes is a common skin anaerobe that is implicated in these organisms are found in the terminal ileum.
the pathogenesis of acne. The colon is the major location of bacteria in the body.
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The yeast Candida albicans is also a member of the nor- Roughly 20% of the feces consists of bacteria, approximately
mal flora of the skin. It can enter a person’s bloodstream 1011 organisms/g. The major bacteria found in the colon are
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when needles pierce the skin (e.g., in patients with intrave- listed in Table 6–3. Note that more than 90% of the fecal flora
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nous catheters or in those who use intravenous drugs). It is are anaerobes, the most important of which is Bacteroides
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an important cause of systemic infections in patients with fragilis. The most abundant facultative bacteria are the coli-
reduced cell-mediated immunity. forms, of which Escherichia coli is the most important.
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CHAPTER 6 Normal Flora 29

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TABLE 6–3 Major Bacteria Found in the Colon reduction of the normal flora for several days, followed by
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a gradual return to normal levels.
Number/g of Important

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Bacterium1 Feces Pathogen
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Bacteroides, especially B. fragilis 1010–1011 Yes NORMAL FLORA OF THE
GENITOURINARY TRACT
10
Bifidobacterium 10 No
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Eubacterium 1010 No
The vaginal flora of adult women consists primarily of Lac-
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7 8
Coliforms 10 –10 Yes
tobacillus species (see Table 6–2). Lactobacilli are respon-
Enterococcus, especially E. faecalis 107–108 Yes sible for producing the acid that keeps the pH of the adult
Lactobacillus 107 No woman’s vagina low. Before puberty and after menopause,
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6 when estrogen levels are low, lactobacilli are rare and the
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Clostridium, especially C. perfringens 10 Yes
vaginal pH is high. Lactobacilli appear to prevent the

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Bacteroides, Bifidobacterium, and Eubacterium (which make up more than 90% of
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the fecal flora) are anaerobes. Coliforms (Escherichia coli, Enterobacter species, and growth of potential pathogens, since their suppression by
antibiotics can lead to overgrowth by C. albicans. Over-
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other gram-negative organisms) are the predominant facultative anaerobes.
growth of this yeast can result in Candida vaginitis.
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The normal flora of the intestinal tract plays a signifi- The vagina is located close to the anus and can be colo-
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cant role in extraintestinal disease. For example, E. coli is nized by members of the fecal flora. For example, women
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the leading cause of urinary tract infections, and B. fragilis who are prone to recurrent urinary tract infections harbor
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is an important cause of peritonitis associated with perfora- organisms such as E. coli and Enterobacter in the introitus.
tion of the intestinal wall following trauma, appendicitis, or About 15% to 20% of women of childbearing age carry
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diverticulitis. Other important anaerobic pathogens include group B streptococci in the vagina. This organism is an
Fusobacterium and Peptostreptococcus, and other important important cause of sepsis and meningitis in the newborn
facultative bacteria include Enterococcus faecalis, which and is acquired during passage through the birth canal. The
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causes urinary tract infections and endocarditis, and Pseu- vagina is colonized by S. aureus in approximately 5% of
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domonas aeruginosa, which can cause various infections, women, which predisposes them to toxic shock syndrome.
particularly in hospitalized patients with decreased host Urine in the bladder is sterile in the healthy person, but
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defenses. P. aeruginosa is present in 10% of normal stools, during passage through the outermost portions of the ure-
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as well as in soil and water. thra, it often becomes contaminated with S. epidermidis,
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Antibiotic therapy (e.g., with clindamycin) can suppress coliforms, diphtheroids, and nonhemolytic streptococci.
the predominant normal flora, thereby allowing a rare The area around the urethra of women and uncircumcised
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organism such as the toxin-producing Clostridium difficile men contains secretions that carry Mycobacterium smeg-
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to overgrow and cause severe colitis. Administration of matis, an acid-fast organism. The skin surrounding the
certain antibiotics, such as neomycin orally, prior to gastro- genitourinary tract is the site of Staphylococcus saprophyti-
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intestinal surgery to “sterilize” the gut leads to a significant cus, a cause of urinary tract infections in women.
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PEARLS
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• Normal flora are those microorganisms that are the perma- • Members of the normal flora are low-virulence organisms. In
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nent residents of the body that everyone has. Some people their usual anatomic site, they are nonpathogenic. However, if
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can be colonized, either transiently or for long periods, with they leave their usual anatomic site, especially in an immuno-
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certain organisms, but those are not considered members of compromised individual, they can cause disease.
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the normal flora. Carriers (also called chronic carriers) are • Colonization resistance occurs when members of the normal
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those individuals in whom pathogenic organisms are present flora occupy receptor sites on the skin and mucosal surfaces,
in significant numbers and therefore are a source of infection
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thereby preventing pathogens from binding to those

for others. receptors.
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• Normal flora organisms are either bacteria or yeasts. Viruses,

protozoa, and helminths are not considered to be members of Important Members of the Normal Flora
the normal flora (but humans can be carriers of some of these
• Skin. The predominant member of the normal flora of the skin
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organisms).
is S. epidermidis. It is an important cause of infections of pros-
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• Normal flora organisms inhabit the body surfaces exposed to

thetic heart valves and prosthetic joints. C. albicans, a yeast
the environment, such as the skin, oropharynx, intestinal
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also found on the skin, can enter the bloodstream and cause
tract, and vagina. Members of the normal flora differ in num-
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disseminated infections, such as endocarditis in intravenous

ber and kind at various anatomic sites.
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30 PART I Basic Bacteriology
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drug users. S. aureus is also present on the skin, but its main outside of the colon. The two most important members of the

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site is in the nose. It causes abscesses in the skin and in many colonic flora that cause disease are the anaerobe B. fragilis and
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other organs. the facultative E. coli. E. faecalis, a facultative, is also a very
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• Oropharynx. The main members of the normal flora of the important pathogen.
mouth and throat are the viridans streptococci, such as S. • Vagina. Lactobacilli are the predominant normal flora organ-
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sanguinis and S. mutans. Viridans streptococci are the most isms in the vagina. They keep the pH of the vagina low, which
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common cause of subacute endocarditis. inhibits the growth of organisms such as C. albicans, an impor-
• Gastrointestinal tract. The stomach contains very few organ- tant cause of vaginitis.
isms because of the low pH. The colon contains the largest • Urethra. The outer third of the urethra contains a mixture of
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number of normal flora and the most diverse species, includ- bacteria, primarily S. epidermidis. The female urethra can
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ing both anaerobic and facultative bacteria. There are both become colonized with fecal flora such as E. coli, which predis-

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gram-positive and gram-negative rods and cocci. The members poses to urinary tract infections.
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of the colonic normal flora are an important cause of disease
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SELF-ASSESSMENT QUESTIONS 4. An outbreak of postsurgical wound infections caused by S.
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aureus has occurred in the hospital. The infection control
1. The colon is the site of the largest number of normal flora team was asked to determine whether the organism could be
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bacteria. Which one of the following bacteria is found in the carried by one of the operating room personnel. Using your
greatest number in the colon? knowledge of normal flora, which one of the following body
(A) Bacteroides fragilis sites is the most likely location for this organism?
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(B) Clostridium perfringens (A) Colon
(C) Enterococcus faecalis (B) Gingival crevice
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(D) Escherichia coli (C) Mouth
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(E) Lactobacillus species (D) Nose
2. A 76-year-old woman with a prosthetic (artificial) hip comes (E) Throat
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to you complaining of fever and pain in that joint. You are
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concerned about an infection by S. epidermidis. Using your
knowledge of normal flora, what is the most likely source of ANSWERS
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this organism?
(A) Dental plaque 1. (A)
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(B) Mouth 2. (C)
3. (C)
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(C) Skin
(D) Stomach 4. (D)
(E) Vagina
3. Your patient is a 30-year-old woman with a previous history
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of rheumatic fever who has had fever for the past 2 weeks. PRACTICE QUESTIONS: USMLE &
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On examination, you find a new heart murmur. You suspect COURSE EXAMINATIONS
endocarditis and do a blood culture, which grows a viridans
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group streptococcus later identified as S. sanguinis. Using Questions on the topics discussed in this chapter can be
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your knowledge of normal flora, what is the most likely found in the Basic Bacteriology section of Part XIII:
USMLE (National Board) Practice Questions starting on fre
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source of this organism?

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page 709. Also see Part XIV: USMLE (National Board)
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(A) Duodenum
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(B) Skin Practice Examination starting on page 751.

(C) Throat
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(D) Urethra
(E) Vagina
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