Re: The Normal Flora Of Humans
- From: rpautrey2 <rpautrey2@xxxxxxxxx>
- Date: Sun, 23 Dec 2007 14:09:46 -0800 (PST)
The normal flora of humans(Excerpt) - rpa2
A third example of host-microbe interactions is the community of
microorganisms that live in or on the human body. We cover this
environment because the normal flora of humans tends to be of great
interest to students, which facilitates the learning process. In this
section we will examine the microbes present on our bodies and discuss
their benefits, which range from supplying nutrients to stimulating
capillary growth and the immune system.
The brain, muscle, kidneys, liver, heart and other tissues of the
healthy host are normally free of microorganisms. However, the outside
surfaces (skin and mucous membranes) are readily colonized by a large
variety of bacteria. The mixture of microbes present in a healthy
individual is termed its normal flora. In many cases, both host and
microbe benefit from these interactions, and for the most part, these
are mutualistic relationships. However, with the help of the immune
system, the body works hard to limit the penetration of the normal
flora beyond these outside surfaces.
From the microbes perspective, the human body is not a homogeneous
environment, but is composed of numerous microenvironments. The normal
flora of each area is specifically adapted to these microenvironments,
because each microbe has a predilection for certain tissues (a tissue
tropism), due to the availability of a favored nutrient or ability to
survive a detrimental aspect of the environment, i.e., acidity or
dryness. As a consequence, the microbes have evolved surface receptors
that support a specific biochemical interaction between them and
particular cell surfaces in those tissues. The mechanisms of these
attachments are probably similar among all microorganisms that
interact with humans, both the normal flora and pathogenic organisms.
Several different host factors also influence the normal flora found
on various parts of the body (Figure 14-11). Traits such as age, sex,
diet and temperature affect the types and number of normal flora. For
example, the onset of puberty increases the secretion of oils from the
sebaceous glands on the skin. This in turn provides nutrients to acne-
causing bacteria that may then flourish in pores, causing infections.
Personal hygiene also affects the normal flora, with the frequency of
washing and tooth brushing affecting the number and types of
microorganisms present in any given area. Finally, genetics also must
play a role, since different people obviously have different
physiological properties that can affect microbial growth. Further
examples will be highlighted as we progress through the various areas
of the body.
The normal human is host to 1012 bacteria on the skin, 1010 in the
mouth and 1014 in the gastrointestinal tract. This latter number far
exceeds the 1013 human cells in our bodies. In a sense, humans and
other large animals are not single beings as much as host-microbial
communities. In this section we will examine the major environments
that the normal flora occupy.
Figure 14-11 The normal flora
Figure Description: The diagram above shows the microorganisms
commonly associated with a healthy adult.
Author note: Have this be a anatomical drawing that you can mouse over
that reveals the bacteria that are present in an area. Gram stains of
some of them would be a nice touch
Skin
The skin of an average adult has an area of approximately two square
meters with about 11012 bacteria. The number and types of
microorganisms present varies with location and moisture content, with
moist areas like the armpits and groin having a different and larger
population of microbes due to the higher water content. Other areas of
the skin are drier and support 100 to 1000 bacteria per square
centimeter of skin. All of these bacteria are found on the top layers
of the skin and hair follicles and rarely penetrate below the surface.
The normal flora of the skin consists mostly of corynebacteria,
staphylococci and Propionibacterium acnes. These microbes generally
form non-pathogenic commensal interactions, which is a dynamic
process. Carriers of Staphylococcus aureus, a potential pathogen, may
harbor this organism on their skin and in the throat, and under
certain circumstances this can lead to disease. The flora changes near
the various orifices of the body (e.g., mouth, nose and anus). Not
surprisingly, the bacteria will be similar to those found within the
orifice.
Conjunctiva
The eye is kept healthy and free of organisms by secretions from the
lacrimal glands. This moist environment would seem attractive, but the
fluid contains lysozyme (an enzyme that degrades peptidoglycan) and
thus is harmful to most bacteria. The eye is also continually cleared
every few seconds by blinking. Due to the above properties, the number
of bacteria found on the conjunctiva is small, but may contain
Staphylococcus aureus, S. epidermidis and corynebacteria. Large
numbers of microorganisms in the eyes may cause a condition termed
conjunctivitis, which evokes an immune response and is associated with
redness and irritation. Several microbes can cause conjunctivitis
including, streptococci, staphylococci and Haemophilus influenzae.
Mouth
The population of microorganisms present in the mouth is large and
complex, reaching levels as high as 1010 bacteria per ml of saliva. As
mentioned earlier, the mouth is a great environment for
microorganisms. There are numerous surfaces in the mouth for
attachment and it is comparatively easy to evade the host immune
system, since it is understandably less active than in the blood and
organs.
More than 200 species of oral bacteria are present in the mouth
including streptococci, lactobacilli, staphylococci and
corynebacteria, with a great number of strict anaerobes, especially
bacteroides. It may seem odd to have strict anaerobes in an
environment that is constantly exposed to oxygen, but realize that the
microbes only respond to their immediate microenvironment. There are
numerous niches inside the mouth that are anaerobic due to the action
of rapidly respiring microbes and the inability of oxygen to diffuse
into certain areas (e.g., the area between the teeth and gums or under
a layer of plaque). It is also clear that oral bacteria cooperate to
form biofilms that not only affect aerobic environments, but also the
ability of host defenses to attack members of the microbial community.
The flora of the mouth and digestive tract change with age and diet.
In the newborn the mouth consists solely of soft tissues (e.g.,
tongue, lips, cheeks and palate). These tissues are sterile at birth,
but are rapidly colonized by Streptococcus salivarius, which makes up
98% of the bacteria present. Eruption of the teeth causes a dramatic
change in the microbes present by providing non-epithelial surfaces,
which are required for colonization by S. mutans and S. sanguis. The
interface between the gums and teeth also creates an area for
anaerobic bacteria to thrive in. The complexity of the mouth flora
increases as the variety of foods consumed expands. The onset of
puberty, with its changes in hormone cycles, correlates with
colonization by Bacteroides and spirochetes.
Most of these organisms are not pathogenic, but under special
circumstances can cause illness. Oral bacteria can cause infections in
the jaw, lungs, heart, brain and extremities when they gain entrance
to tissues through surgical wounds or other injuries. However, more
common maladies perpetrated by the normal flora of the mouth include
dental plaque, dental carries and periodontal disease. These maladies
are arguably the most significant negative impact of the normal flora
on the human body and we will spend a bit of time examining the
microbes involved.
Plaque is a build-up of material on the teeth, and 60% of this
material is microbial (Figure 14-12). It is a naturally constructed
biofilm that may reach a thickness of 300-500 bacteria on the surface
of the teeth. The instigators of plaque and the most numerous bacteria
contained therein are S. mutans and S. sanguis. The attachment of
these microbes to the teeth and tissues is a two-step process. The
microbes initially establish a weak attachment to salivary
glycoproteins and form a thin film on the surface of the teeth. This
is followed by a much stronger attachment through sticky extracellular
polymers (glucans) synthesized by glycosyltransferase. The amount of
this polymer formed is dependent upon the availability of hexose
sugars (principally sucrose) in the diet, and this is why the
consumption of sugar leads to plaque and potentially to tooth decay.
Fig 14-12 The consortia that form on teeth
Author note: Include appropriate bacteria near the enamel etc.
Dental carries involves the destruction of the enamel and related
parts of the teeth due to bacterial activity. Microorganisms present
in the plaque catabolize sugar to lactic acid or other acids that
destroy the enamel of the teeth. These activities are most often
carried out by S. mutans, which is capable of withstanding the low pH
resultant from acid production, but other lactic acid bacteria can
also participate. After initial enamel destruction, termed
demineralization, various oral bacteria gain access to interior
regions of the tooth, including lactobacilli, Actinomyces and other
proteolytic bacteria. These microbes contribute to the progression of
the lesions.
Periodontal disease results from infection of the various supporting
structures of the teeth due to prolonged periods of plaque formation.
The most common form of this disease is gingivitis, an inflammation of
the gums, caused by increased populations of Actinomyces and other
anaerobic bacteria. Gingivitis does not normally lead to tooth loss.
In the most serious forms of periodontal disease, microbes gain access
to the periodontal membrane under the teeth and the bone in the jaw,
causing painful infections and tooth loss. Bacteria in these lesions
are complex populations including Actinomyces, streptococci,
spirochetes and Bacteroides. The mechanisms of tissue destruction are
not clearly defined, but hydrolytic enzymes, endotoxins and other
toxic bacterial metabolites seem to play a role.
Respiratory tract
The respiratory tract consists of the nostrils, the nasopharynx (the
area behind the nose), trachea. larynxand the lungs. Microorganisms
colonize these areas due to their high water activity, plentiful
nutrients and constant temperature. Aerobic, aerotolerant and,
somewhat surprisingly, even strictly anaerobic bacteria heavily
colonize the nostrils. Many different bacteria are capable of thriving
in this environment, including Staphylococcus epidermidis,
streptococci, neisseriae and corynebacteria. About 20% of the general
population are carriers of Staphylococcus aureus, and the nares are
the major reservoir of this pathogen. In contrast, the sinuses are
typically free of microorganisms.
The nasopharynx also contains a large number and variety of gram-
positive and gram-negative bacteria, including streptococci,
neisseriae, Bacteroides and Pseudomonas spp., enteric rods,
actinomycetes and Mycoplasma sp.. The nasopharynx often also harbors
several important pathogens, including Streptococcus pyogenes,
Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus
influenzae. The presence of these pathogens in the nasopharynx
normally poses no problem for the host. It is only when these microbes
penetrate other areas such as the ears, sinuses, lungs, eyes or the
brain that disease occurs.
The lower respiratory tract is normally free of microorganisms because
of the action of the ciliated epithelium and a sticky mucus that
covers the lining of the bronchial tubes. The mucus traps bacterial
that penetrate into the lungs and the upward action of the beating
cilia then moves them out to be sneezed, coughed or swallowed. Damage
to this protective barrier bronchitis or smoking invites colonization
by pathogens in the upper respiratory tract and increases the
likelihood of infections of the lower respiratory tract.
Gastrointestinal tract
The microbial flora of the gastrointestinal (GI) tract is the most
extensively studied group of organisms that inhabit our bodies. Large
collections of microorganisms flourish in the nutrient-rich
environment that our digestive system provides. The GI tract can be
broken into four areas: the upper GI tract, the stomach, the small
intestine and the large intestine. Generally, the numbers of kinds of
flora in the GI tract increase as one moves from the upper GI to the
large intestine and also across the tract, where certain bacteria
attach to the GI epithelium and others occur in the lumen. Often there
is a strong association between specific bacteria and gut tissues or
cells. For example, gram-positive bacteria, such as streptococci and
lactobacilli most likely adhere to the walls of the intestine using
polysaccharides or lipoteichoic acids. Enteric and other gram-negative
bacteria will utilize specific fimbriae on their cell surface. In both
cases, these bacterial macromolecules bind to specific receptors on
cells of the GI tract. This tissue tropism may partially account for
the kinds of microbes found and their relative numbers in various
parts of the gut. In addition, the higher populations later in the gut
may be due to the greater time spent in the latter portions of the GI
tract.
Upper GI and Stomach
Most microbes are rapidly moved into the stomach because of the
powerful peristaltic action of swallowing, so the microbial content of
the upper GI tract is primarily whatever is swallowed. Once in the
stomach, the high acidity kills all but the most acid-tolerant (mainly
streptococci). Now one might wonder how the lower GI becomes populated
with acid-sensitive bacteria if stomach acid is such a barrier. The
answer is that, as in most situations in biology, the result is a
statistical one. Certainly the vast majority of acid-sensitive
bacteria are killed, but with a low probability, some manage to make
it through the stomach and establish a residence in the less hostile
intestine. Obviously, this is a function of the degree of sensitivity,
the food they are associated with and the number of bacteria that we
ingest.
Insert Sidebar
Salmonellosis (caused by Salmonella enterica) is one of the leading
causes of food-borne diarrheal diseases in the world. The source of
infection is most often from food animals that are seemingly healthy
carriers of the microbe. Consumption of poorly prepared meat or eggs
from these infective animals allows the transmission of S. enterica
into the gastrointestinal tract where they cause disease. Efforts have
been made to develop methods to eradicate Salmonella in these feed
animals, since the microbe is not important in their health.
Several methods have shown promise. The spraying of newly hatched
chicks with a mixture of harmless bacteria has greatly reduced
Salmonella infection in the birds. The harmless bacteria in the spray
prevent colonization of the bird by Salmonella. Several oral vaccines
against Salmonella elicit an immune response against the microbe and
greatly reduce colonization. With application of these methods and
strict policies regulating infected feed animals, it may be possible
to greatly reduce the incidence of Salmonellosis in the world.
End sidebar
Small intestine
Microbial populations are much higher in the proximal end of the small
intestine than in the stomach, but they are still relatively sparse
(105 to 107 per gram) in comparison to the rest of the intestines
(Figure 14-14). Gram-positive bacteria, consisting mainly of
lactobacilli and Enterococcus faecalis inhabit this part of the GI
tract. The distal end of the small intestine, which can have bacterial
populations up to 108 bacteria per ml, contains similar species, but
at higher numbers. Enteric rods and Bacteroides also colonize this
part of the GI tract.
This is an area of the body that shows a very clear positive impact of
the presence of bacteria. For unknown reasons, capillaries in the
intestines of animals do not develop fully unless there are bacteria
present. This poor development leads to poor utilization of nutrients
by the body and generally poor development. Intestinal bacteria also
metabolize some compounds that we cannot, which leads to more
efficient utilization of food. Finally, they synthesize vitamins K and
B complex and provide these essential compounds to us.
On the negative side, bacteria in this region can metabolize compounds
to end products that might be a problem, such as the creation of
carcinogens. As elsewhere in the body, they can also serve as
opportunistic pathogens should there be damage to the intestinal wall.
Figure 14-13 The GI tract with organisms present in each section
Large intestine
The inhabitants of the large intestine are qualitatively similar to
those found in feces, though more populous, with numbers reaching 1011
cells per gram. Up to 1,000 species are represented, including enteric
rods, streptococci, clostridia and lactobacilli. The predominant
species by far are the strictly anaerobic Bacteroides and
bifidobacteria that outnumber E. coli 1,000:1 to 10,000:1. It is now
known that the human colon contains many anaerobic methanogenic
bacteria - up to 1010 per gram. Their benefits and potential problems
are similar to what was described above.
Urogenital tract
The urogenital tract consists of the bladder, the ureter, the urethra
and the genitalia. The bladder and internal regions of the ureter and
urethra are typically devoid of microorganisms. The few found in urine
cultures are probably contaminants from end of the urethra and the
genitals, which have bacteria that are common on the skin and the
colon. These include S. epidermidis, Enterococcus faecalis, E. coli,
Proteus spp., corynebacteria and streptococci.
The vagina of the healthy female is colonized soon after birth by
typical microbes found on the skin and rectum, including
corynebacteria, staphylococci, non-pyogenic streptococci, E. coli, and
a lactic acid bacterium named Dderleins bacilli (most
likely,Lactobacillus acidophilus). After the onset of puberty and
throughout reproductive life, circulating estrogen causes the
secretion of glycogen in the vagina. Metabolism of glycogen to lactic
acid by Dderleins bacilli drops the pH and inhibits colonization by
all except this microbe and a few others. Significantly, this helps
prevent colonization by Candida albicans, the cause of yeast
infections.
Benefits of the normal flora
Many microorganisms enjoy the lush environment our bodies provide for
them, but what are the benefits for the host?
Probably the most important benefit of the normal flora is that they
take up space and nutrients that could otherwise be used by
pathogens.
The normal flora also actively antagonize pathogens by producing
substances that inhibit or kill them. They produce substances ranging
from non-specific fatty acids and peroxidases to highly specific
bacteriocins that inhibit or kill other bacteria.
The presence of the normal flora provides constant stimulation of the
immune system, and the products of this stimulation will sometimes
cross-react with pathogenic species. These immune responses also help
to fight opportunistic infections by the normal flora. This is a very
important role in the development of our immune systems.
The normal flora seems to be important in the development of gut-
associated lymphoid tissue (part of the immune system) as shown by
studies of germ-free animals. These animals have underdeveloped immune
tissues and immunological stimulation is weak when challenged with
pathogens.
As mentioned above, normal flora enhances capillary development.
Members of the normal GI flora synthesize vitamin K and some of the B
vitamins, which are absorbed into the bloodstream. Studies with germ-
free animals show a nutritional deficit for vitamin K and the B
vitamins suggesting that we absorb these vitamins from the GI tract
and use them in our metabolism.
As noted in the text, however, the presence of microbes is not without
a cost. Their metabolism allows them to attack a broad variety of
compounds in our diets, some of which they can convert to compounds
that are harmful to us. They can be opportunistic pathogens whenever
luck or injury allows them into regions of the bodies where they are
not wanted.
Items in the microbiology textbook are copyright, Timothy Paustian©
1999-2006.
.
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