NORMAL FLORA OF THE HUMAN BODY

The mixture of organisms regularly found at any anatomical site is referred to as the
normal
flora.
The normal flora of humans is exceedingly complex and consists of more than 200
speciesof bacteria.The makeup of the normal flora depends upon various factors,
includinggenetics, age, sex, stress, nutrition and diet of the individual.The normal flora of
humansconsists of a few eukaryotic fungi and protists, and some methanogenic Archaea
thatcolonize the lower intestinal tract,but the Bacteria are the most numerous and
obviousmicrobial components of the normal flora.
Mutualistic Relationship
The normal flora derives from the host a supply of nutrients, a stable
environmentand constant temperature, protection, and transport. The host obtains from
the normal floracertain nutritional benefits, stimulation of the immune system, and
colonization strategiesthat exclude potential pathogens at the site.
The normal flora are obviously adapted to their host (tissues), most probably by
biochemicalinteractions between bacterial surface components (ligands or adhesins)
and host cellmolecular receptors.
In general, there are three explanations for why the normal bacterial flora are located at
particularanatomicalsites.
1. The normal flora exhibit a tissue preference or predilection for colonization. This
isreferred to as tissue tropism .One explanation for tissue tropism is that the host
providesan essential growth factor needed by the bacterium. Of course, to explain why
bacteria arenot at an alternative site, the host inherently provides an inhospitable
environment for thebacterium by the production of such substances as stomach acids,
bile salts and lysozyme.
2. Many of the normal flora are able to specifically colonize a particular tissue or
surfaceusing their own surface components like capsules, fimbriae, cell wall
components, asspecific ligands for attachment to specific receptors located at the
colonization site.
3. Some of the indigenous bacteria are able to construct bacterial biofilms on a
tissuesurface, or they are able to colonize a biofilm built by another bacterial
species.Manybiofilms are a mixture of microbes, although one member is responsible for
maintaining the biofilm and may predominate

THE COMPOSITION OF THE NORMAL FLORA

It has been calculated that the normal human is host to about 1012 bacteria on the skin,
1010
in the mouth, and 1014 in the gastrointestinal tract.
Normal Flora of the Skin.
An adult is covered with approximately 2 square meters of skin. The density
andcomposition of the normal flora of the skin vary with anatomical locale. The high
moisture ofcontent of the axilla, the groin, and the skin between the toes and near
orifices supports theactivity and growth of relatively high densities of bacterial cells, but
at most other sites thebacterial population is fairly low, generally in 100s or 1000s per
square cm.
The majority of skin microorganisms are found in the most superficial layers of the
epidermisand the upper parts of the hair follicles. They consist largely ofStaphylococcus
epidermidisandMicrococcus spp and corynebacteria. These are generally
nonpathogenic andconsidered to be commensal, although mutualistic and parasitic roles
have been assignedto them. For example, skin bacteria or their metabolites may protect
against colonization bydermatophytic fungi and/or bacterial metabolites on the skin may
contribute to thedevelopment of certain skin cancers. Sometimes potentially
pathogenicStaphy lococcus
aureus is found on the face and hands, particularly in individuals who are nasal carriers.
Qualitatively, the bacteria on the skin near any body orifice may be similar to those in the
orifice.
Normal Flora of the Respiratory Tract.
The nares (nostrils) are always heavily colonized, predominantly withStaphy lococcus
epidermidis and corynebacteria, and often (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. A large number of bacterial species colonize
theupper respiratory tract (nasopharynx) and includes predominantly non-hemolytic and
alpha-hemolytic streptococci andNeisseria species and sometimes pathogens such as
Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis.
The lower respiratory tract (trachea, bronchi, and pulmonary tissues) is virtually free
ofmicroorganisms, 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 bythe action of the mucociliary blanket that lines the bronchi, to be
removed subsequently bycoughing, sneezing, swallowing, etc. If the respiratory tract
epithelium becomes damaged,as in bronchitis or viral pneumonia, the individual may
become susceptible to infection bypathogens descending from the nasopharynx (e.g. H.
influenzae or S. pneumoniae
Normal Flora of the Human Oral Cavity.
The presence of nutrients, epithelial debris, and secretions makes the mouth a
favorablehabitat 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
thiscorresponds with changes in the composition of the normal flora. At birth the oral
cavity iscomposed solely of the soft tissues of the lips,cheeks, tongue and palate, which
are keptmoist by the secretions of the salivary glands. At birth the oral cavity is sterile
but rapidlybecomes 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
firstyear leads to colonization by S. mutans and S. sanguis. These bacteria require
anondesquamating (nonepithelial) surface in order to colonize. They will persist as long
asteeth remain. Other strains of streptococci adhere strongly to the gums and cheeks but
notto 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 oralflora continues to increase with time, andBacteroides and spirochetes colonize
around
The normal flora occupy available colonization sites which makes it more difficult for
othermicroorganisms (nonindigenous species) to become established. Indigenous oral
floracontribute to host nutrition through the synthesis of vitamins. Indigenous flora of the
mouthcontribute to immunity by inducing low levels of circulating and secretory
antibodies thatmay cross react with pathogens. Oral bacteria exert microbial antagonism
against certainpathogens by production of fatty acids, peroxides, bacteriocins, etc. which
inhibit or killnonindigenous species
The normal oral bacterial flora of humans may harm their host since some of these
bacteriaare parasites which possess pathogenic potential. If certain oral bacteria are
able to invadetissues not normally accessible to them characteristic diseases result. For
example, oralorganisms gaining entrance into tissues (e.g. via surgical wounds) may
cause abscesses ofalveolar bone, lung, brain or the extremities. Such infections usually
contain mixtures ofbacteria with Bacteroides melaninogenicus often playing a dominant
role. Also, oralstreptococci may be introduced into wounds created by dental
manipulation or treatment. Ifthis occurs in an individual with damaged heart valves due
to rheumatic fever (previouslyinduced by streptococci), the oral streptococci may adhere
to the damaged heart valves and
Dental plaque, dental caries and periodontal disease in humans result primarily from
actionsinitiated by the normal bacterial flora. Dental plaque, which is material adhering to
the teeth,consists of bacterial cells (60-70% the volume of the plaque), salivary
polymers, andbacterial extracellular products. Plaque is a naturally-constructed biofilm,
in which theconsortia of bacteria may reach a thickness of 300-500 cells on the surfaces
of the teeth.These accumulations subject the teeth and gingival tissues to high
concentrations ofbacterial metabolites, which result in dental disease.
By far the dominant bacterial species in dental plaque are Streptococcus sanguis and
Streptococcus mutans, both of which are considered responsible for plaque.
Streptococcus mutans has a number of physiological and biochemical properties which
are
consistent with its ability to initiate and mediate dental caries. S. mutans is a
regularcomponent of the normal oral flora of humans and it occurs in relatively large
numbers.Numbers of S. mutans in saliva are correlated with the incidence of dental
caries. It readilycolonizes tooth surfaces: salivary components (mucins, which are
glycoproteins) form a thin
film on the tooth called the enamel pellicle. The adsorbed mucins are thought to serve as
molecular receptors for ligands on the bacterial cell surface.
S. mutans readily colonizes tooth surfaces: salivary components (mucins, which are
glycoproteins) form a thin film on the tooth called the enamel pellicle. The
adsorbedmucins are thought to serve as molecular receptors for ligands on the bacterial
cell surface.
S. mutans contains the enzyme glycosyl transferase that probably serves as the
bacterial ligand for attachment, and that polymerizes glucose obtained from dietary
sucrose to glucans which leads directly to the formation of plaque.
S. mutans produces lactic acid from the utilization of dietary carbohydrate which
demineralizes tooth enamel. S. mutansproduces more lactic acid and is more acid-
tolerant than most other streptococci.
S. mutans stores polysaccharides made from dietary sugars which can be utilized as
reserve carbon and energy sources for production of lactic acid. The
extracellularglucans formed by S. mutans are, in fact, bacterial capsular polysaccharides
thatfunction as carbohydrate reserves. The organisms can also form
intracellularpolysaccharides from sugars which are stored in cells and then metabolized
to lactic acid
Streptococcus mutans appears to be important in the initiation of dental caries because
its activities lead to colonization of the tooth surfaces, plaque formation, and
localizeddemineralization of tooth enamel. It is not however, the only cause of dental
decay. Afterinitial weakening of the enamel, various oral bacteria gain access to interior
regions of thetooth. Lactobacilli,Actinomyces, and various proteolytic bacteria are
commonly found inhuman carious dentin and cementum, which suggests that they are
secondary invaders thatcontribute to the progression of the lesions.
Periodontal diseases are bacterial infections that affect the supporting structures of the
teeth(gingiva, cementum, periodontal membrane and alveolar bone). The most common
form,gingivitis, is an inflammatory condition of the gums. It is associated with
accumulations ofbacterial plaque in the area. Increased populations ofActino
myces have been found, and

Normal Flora of the COnjunctiva.

A variety of bacteria may be cultivated from the normal conjunctiva but the number
oforganisms is usually small. Staphylococcus epidermidis and certain
coryneforms(Propionibacterium acnes) are dominant. Staphylococcus aureus, some
streptococci,
Haemophilus spp. and Neisseria spp. are occasionally found. The conjunctiva is kept
moist
and healthy by the continuous secretions from the lachrymal glands. Blinking wipes
theconjunctiva every few seconds mechanically washing away foreign objects
includingbacteria. Lachrymal secretions (tears) also contain bactericidal substances
includinglysozyme. There is little or no opportunity for microorganisms to colonize
theconjunctiva.without special mechanisms to attach to the epithelial surfaces and some
abilityto withstand attack by lysozyme. Pathogens which do infect the conjunctiva
(e.g.Ne isseria gonorrhoeaeand Chlamydia trachomatis ) are thought to be able to
specifically attach to the conjunctival epithelium by means of sialic acid receptors on
epithelial cells, but this is not
certain.
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 theanterior urethra, as indicated principally by urine cultures, suggests that the
area my beinhabited by a relatively consistent normal flora consisting of Staphylococcus
epidermidis,
Streptococcus(Enterococcus)faecalis, and some alpha-hemolytic streptococci. There
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, mayoccasionally be found at the anterior urethra.
The vagina becomes colonized soon after birth with corynebacteria,
staphylococci,nonpyogenic streptococci, E. coli, and a lactic acid bacterium named
"Doderlein's bacillus"(probably 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. Thelactic acid and other products of metabolism inhibit
colonization by all except Doderlein'sbacillus and a select number of bacteria. The
resulting low pH of the vaginal epitheliumprevents establishment of most bacteria and
the potentially pathogenic yeast,Candida albicans.

Normal Flora of the Gastrointestinal Tract.

The bacterial flora of the GI tract of animals has been studied more extensively than that
of any other site. And this does not consider all the studies on the colon
bacteriumEscherichia coli, which is a favorite experimental organism for microbiologists,
geneticists, and molecular biologists! The composition of the GI flora differs between
various animal species, and withinindividual animal species. In humans, the composition
of the flora is also influenced by age,diet and cultural conditions. The following table
shows the distribution of some commonintestinal bacteria in various animal species
including humans.
In the upper GI tract of adult humans, the esophagus contains only the bacteria
swallowedwith saliva and food. Because of the high acidity of the gastric juice only a few
bacteria(mainly lactobacilli) can be cultured from the normal stomach.
The proximal small intestine has a relatively sparse Gram-positive flora, consisting
mainly oflactobacilli and Streptococcus faecalis This region has about 105 - 107 bacteria
per ml offluid. The distal part of the small intestine contains greater numbers of bacteria
(108/ml) andadditional species including coliforms and Bacteroides, in addition to
lactobacilli and streptococci.
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 moreprominent, and streptococci, clostridia and lactobacilli can be regularly
found, but thepredominant species are anaerobic Bacteroides and certain anaerobic
lactobacilli(Bifidobacteria). These organisms may outnumber E. coli by 1,000:1 to
10,000:1. It is now known that significant numbers of anaerobic methanogenic bacteria
(up to 1010/gm) also
reside in the colon of humans.
At birth the entire intestinal tract is sterile, but bacteria enter with the first feed. The
initialcolonizing bacteria vary with the food source of the infant. In breast-fed infants
bifidobacteriaaccount for more than 90% of the total intestinal
bacteria.Enterobacteriaceae and fecalstreptococci are regularly present, but in low
proportions, while bacteroides, staphylococci,lactobacilli and clostridia are practically
absent. In bottle-fed infants bifidobacteria are notpredominant. When breast-fed infants
are switched to a diet of cows milk or solid food,bifidobacteria are progressively joined
by enterics, bacteroides, streptococci lactobacilli andclostridia.
The composition of the flora of the gastrointestinal tract varies along the tract (at
longitudinallevels) and across the tract (at horizontal levels) where certain bacteria
attach to thegastrointestinal epithelium and others occur in the lumen. There is
frequently a very closeassociation between specific bacteria in the intestinal ecosystem
and specific gut tissues orcells (evidence of tissue trophism). Gram-positive bacteria,
such as the streptococci andlactobacilli, are thought to adhere to the gastrointestinal
epithelium using polysaccharidecapsules or wall lipoteichoic acids to attach to specific
receptors on the epithelial cells.Likewise, Gram-negative bacteria such as the enterics
may attach by means of specific fimbriae on the bacterial cell which bind to glycoproteins
on the epithelial cell surface

The following benefits to a human of a conventional intestinal flora are often named:
Normal flora synthesize and excrete vitamins in excess of their own needs, whichcan be
absorbed as nutrients in the host. For example, E. coli secretes Vitamin Kand certain B-
vitamins. Germ-free animals may be deficient in Vitamin K to theextent that it is
necessary to supplement their diets.
The normal flora prevent colonization by pathogens by competing for attachment
sites or for essential nutrients.
The normal flora may antagonize other bacteria through the production ofsubstances
which inhibit or kill nonindigenous species. The intestinal bacteriaproduce a variety of
substances ranging from relatively nonspecific fatty acids andperoxides to highly specific
bacteriocins which inhibit or kill other bacteria.
The normal flora stimulate the development of certain tissues, i.e., the caecum
andcertain lymphatic tissues in the GI tract. The caecum of germ-free animals
isenlarged, thin-walled, and fluid-filled, compared to that organ in a conventionalanimal.
Also, based on the ability to undergo immunological stimulation, the intestinallymphatic
tissues of germ-free animals are poorly developed compared to aconventional animals.
The normal flora stimulate the production of cross-reactive antibodies. It is knownthat the
normal flora behave as antigens in an animal and therefore induceimmunological
responses. Conceivably low levels of antibodies produced againstcomponents of the
normal flora could cross react with certain related pathogens and prevent infection or
invasion