Infections of the Gastrointestinal Tract
I. The digestive system or gastrointestinal tract (GI tract)
consists of a "tube" that runs from the mouth to the anus (alimentary
canal). This "tube" is divided into the oral cavity, esophagus, stomach,
small intestine and large intestine. Several organs are not part of this tube but
contribute secretions to the alimentary canal. These include the salivary glands, liver
A. The mucous membrane of most the alimentary canal produces and is covered with mucus
and has constant movement of materials through it. This limits the ability of
microorganisms to colonize this tract. Secretions in the mouth are rich in lysosome and
also have IgA. The low pH of the stomach kills most swallowed pathogens. Digestive enzymes
in the small intestine will destroy most of the bacteria and viruses that survived the
B. The large intestine is host to a highly concentrated bacterial population. This
normal flora is a mixed population with members of the family Enterobacteriaceae
(gram negative facultative anaerobes), and obligate anaerobes of the genera Bacterioides
and Clostridium. These organisms complete the digestion of ingested
foods. The presence of these bacteria limits the ability of many pathogens to invade the
body via the distal GI tract.
C. The submucosa of the GI tract is a site with high phagocyte activity and
considerable lymphatic involvement. Nutrients are across the mucosa of the small intestine
and are transported to the liver via the blood and lymphatics (lacteals). In the liver
phagocytic cells known as Kupffer cells ingest and destroy most bacteria
that have invaded. The ileum (last portion of the small intestine) is lined with lymphoid
tissues known as Peyers patches. The Peyers patches and the
movement of materials through the small intestine limit the ability of bacteria to spread
from the large intestine into the small intestine.
II. Cavities in the enamel coating of the teeth are referred to as dental caries.
It is now understood that this disease is caused by the action of the pathogen, Streptococcus
mutans. This organism survives as part of your mouths normal flora. Under
certain conditions it is able to produce acids that will result in the breakdown of a
tooth's enamel covering.
A. S. mutans breaks down sucrose (table sugar) into glucose and
fructose and uses these for energy. It also uses the sucrose to produce a polymer known as
dextran. The bacteria live under this blanket of dextran in a buildup known
as plaque. If not removed the plaque becomes calcified forming what is
referred to as tarter.
1. The microenvironment under the plaque is increasingly anaerobic leading to
metabolism that favors fermentation and thus the production of acids. The acids cause the
enamel to deteriorate to the point where bacteria can gain access to the underlying pulp,
blood vessels and nerve. Once into these areas the infection can lead to necrosis of the
inner tissues of the tooth.
2. Fluoride reverses this by stabilizing the enamel in such a way that the low pH has
B. Accumulation of plaque at the gum line can lead to the inflammation of the gums
known as periodontal disease. This condition can progress leading to
destruction of the bone that supports the teeth. Bacteria present in the inflamed gums do
not appear to penetrate the mucosa. Pathology is the result of the release exoenzymes the
degrade the surrounding tissues. Presence of the bacteria increases the activity of
neutrophils and macrophages. This increased activity leads to the necrosis of the gums and
III. The growth of Staphylococcus aureus in unrefrigerated foods
leads to the release of an exotoxin into the food. Ingestion of this food leads to a
condition known as enterotoxicosis. The toxin is referred to as an enterotoxin
because it exerts its effects upon the digestive tract. This particular enterotoxin
results in nausea, cramping, diarrhea and vomiting. The toxin is absorbed across the
mucosa and acts as a superantigen causing nonspecific activation of T cells. This in-turn
leads to the inappropriate dumping of inflammatory mediators by the gut associated
lymphocytes. Signs and symptoms usually are manifested within several hours of ingestion
of contaminated food and are gone within 10 hours.
A. The organism usually is inoculated into the food from the skin due to improper
handling of the food. Lack of refrigeration leads to growth of the organism and the
production of the toxin. The bacteria themselves usually do not survive the low pH of the
B. The toxin is said to be heat stable. This means that the toxin remains active even
after extended periods of exposure to heat. Thus cooking or reheating foods that are
already contaminated by the toxin will not solve the problem.
IV. During the past decade, Helicobacter
pylori has become recognized as one of the most common human
pathogens, colonizing the gastric mucosa of almost all persons exposed to poor
hygienic conditions from childhood. It also is often found, with a lower
frequency, in groups of high socioeconomic status. H.
pylori causes chronic active gastritis and is a major factor in the
pathogenesis of duodenal ulcers
and, to a lesser extent, gastric
ulcers. In addition, the presence of this bacterium is now recognized as
a risk factor for gastric adenocarcinoma and lymphoma. Nevertheless, most
infections appear without clinical consequences.
A similar organism, Gastrospirillum hominis is though to also play a role in
the development of certain types of gastric ulcer. The relative frequency of infection is much lower for G.
hominis. Be aware that it can also cause gastroenteritis but we will
not discuss this organism any further.
pylori is a gram negative vibrio.
It colonizes the gastric or duodenal mucosa. To colonize it must be able to penetrate the mucus covering
of the epithelium. Once under this
covering it attaches to the surface of the cells and begins multiplying.
Since many persons have the organism present but have no apparent ulcer
problem it is not altogether clear as to how H.
pylori causes the degenerative inflammation which leads to gastric or
duodenal ulcers. Variation in the
virulence (due to variation in presence of certain genes) may play a role in
this unexplained irregularity in pathology.
Production of certain enzymes which allow the bacterium to better survive
in the hostile environment also produce byproducts which are injurious to the
mucosa of the stomach or small intestine. This
may increase the rate of cell death around organism expressing these genes and
directly or indirectly lead to the ulceration of the mucosa.
Certain strains of H. pylori produce a toxin known as vacuolating cytotoxin. This
toxin has been shown to lead to cell death in laboratory settings.
In most strains isolated from ulcers the gene for this toxin is present.
Diagnosis of infection with this organism may involve culturing the
organism from or direct observation of the organism in tissue biopsied from the
ulcer. The organism appears to have
a highly focal nature consequently negative biopsy results are not always
indicative of lack of infection. The
immune system mounts a strong B cell reaction to this organism.
Consequently serological tests (ELISA) are used to demonstrate the
presence of IgG. It should b noted that due to the widespread nature of
inapparent infection, persons with no signs of ulcerative disease will often
have be seropositive (have a
titer against H. pylori).
The route of transmission is not clear.
Studies indicate that this is a much more widespread organism in the
developing world. Usually this is
indicative of routes of transmission which rely on the oral-fecal route or need
highly crowded conditions (close contact) for transmission.
In this country the age of the person and their socioeconomic status
impact the chances of infection.
Although H. pylori is sensitive to many antimicrobial drugs
in vitro, it is difficult to
eradicate from the stomach. This
may be ascribed to antibiotic breakdown by gastric acid, clearance by gastric
emptying, and the difficult-to-penetrate mucous layer in which the bacterium
resides. Resistance of H. pylori to specific antibiotics, especially metronidazole, is also
frequent. Therefore, it is
generally accepted that a combination of at least two, and possibly three,
antimicrobial agents should be given for a minimum of 1 week.
The regimen found to be most effective is the administration of
amoxicillin (or tetracycline) plus metronidazole and bismuth subsalicylate (peptobismal)
2 to 4 times a day for 2 to 3 weeks . The
combination of a proton pump inhibitor (H+-K+ ATPase antagonist) with
amoxicillin or acid-stable macrolides (clarythromycin or roxithromycin) appears
more promising; a number of studies are being conducted to determine the optimal
dose, duration, concomitant therapy, and cost-effectiveness of these compounds.
Recently, it was shown that at least a 7-day course of any of these regimens is
required to obtain a high (90%) cure rate, but that continuing treatment for
more than 10 days does not significantly improve its efficacy. Finally, topical
therapy for 1h was
recently tried with excellent results, albeit in only one center at this time.
This treatment involves a 2-day administration of a mucolytic agent
to dissolve the mucous layer and of a proton pump inhibitor. On the third
day, a balloon is introduced into the second portion of the duodenum and a
solution of pronase, amoxicillin, metronidazole, and bismuth subsalicylate is
injected into the stomach, where it is left for 1 h. The presence of the
duodenal balloon appears to prevent emptying of the antibiotics and the
mucolytic agent, thus ensuring maximum efficacy of the therapy.
There is mounting evidence that gastric cancers may be linked to
long-term infection with H. pylori. The
mechanism which might be responsible for this are not understood.
V. Infection of the mucosa of the gastrointestinal tract by bacteria is referred to as
bacterial enteritis. These bacteria often produce exotoxins that act upon
the mucus membrane of the gut. These types of exotoxins are also referred to as
enterotoxins. Often the infection results in the loss large amounts of water into the GI
tract or the failure of the large intestine to reabsorb the water from the contents of the
colon. In either case, this results in diarrhea that can lead to dehydration. Though in a
healthy adult this often is little more than an inconvenience, infants, children and
compromised adults can be severely effected by this condition. It is estimated that
somewhere between 5 and 10 million deaths annually are directly attributable to diarrhea.
The majority of these infections are caused by two genera of bacteria: Shigella
A. Members of the genus Campylobacter
are gram negative vibrios which usually occur in pairs.
They are microaerophilic and thus are very slow growing organisms.
There are several Campylobacter species but three are of significance with regard to
human medicine. They include: C.
jejuni, C. coli and C. fetus. All three can be found as part of the normal flora of
the human and/or domestic animal gut (cows, horses, dogs, etc.).
For the most part, infections involve a self limiting gastroenteritis
of varying degrees of severity. But
systemic infection (especially with C.
fetus) can lead to death or fetal loss and requires medical
Campylobacter jejuni is one
of the most common human pathogens. It is estimated that up to 30% of the
gastroenteritis observed in children is due to infection with C.
jejuni. The organism is orally acquired and often is a contaminate of
milk, chicken or other foodstuffs which have been contaminated with animal
wastes. C. jejuni is shed in the feces of the infected human and can be
spread person to person due to poor hygiene.
When ingested, C.
jejuni moves to the ileum (last portion of the small intestine) and
adhere to the surface of the epithelial cells of the mucus membrane.
Release of a toxin (Campylobacter
jejuni toxin or CJT)
leads to the over secretion of electrolytes into the gut.
This results in a diarrhea,
which may be bloody, accompanied by headache, fever and abdominal pain.
Severe cases require treatment involving rehydration therapy.
Campylobacter fetus is much
more invasive. Infection can
lead to spread of the organism from the gut leading to systemic infection.
This can result in septicemia, pneumonia, meningitis and, in pregnant
females, infection of the fetus sometimes leading to a
The gastroenteritis is usually allowed to run its course (no pun
intended) while systemic infections are treated aggressively with
B. Species of the genus Shigella are genetically and morphologically virtually
indistinguishable from E. coli, the gram negative rod that is found in the normal
flora of most humans. Shigella species have retained a different taxonomic
classification due to their ability to cause disease. The bloody diarrhea, cramping and
other symptoms of Shigella infection are referred to as shigellosis or bacillary
1. To cause disease it is believed that the Shigella organism must be able to attach
and be internalized by the cells of the large intestine. Once internalized, the
organism multiplies within the mucosa cells. Usually the organism never spreads out of the
mucosa into the underlying tissues.
2. The infecting Shigella organisms produce a shiga toxin (also
known as vero toxin) that results in the death of the mucosa cell. The toxin binds to the
ribosome of the mucosa cell causing it to be unable to function. The host cell losses the
ability to synthesize proteins. If this toxin spreads systemically, damage to other types
of cells can occur.
3. Infected cells die due to the effects of the toxin or are attacked by the immune
system. The death of the cells and the inflammation caused by cell injury results of an
inability of the large intestine to concentrate the stool. Furthermore lesions produced by
this necrosis result in bleeding into the bowel. The person suffering from this infection
will have diarrhea that is laden with blood and mucus. This is referred to as dysentery.
4. Carriers shed Shigella in their stool for 1-4 weeks after resolution of
clinical signs of infection. Poor sanitation or poor hygiene allows the organism to be
spread within a tightly associated group such as a day-care, hospital or ship.
C. Species of the genus Salmonella (a gram negative rod also) infect a
wide range of host animals. Infection can range from a self limiting (2-5 days) diarrhea
to a much more severe disease known as typhoid fever or an equally severe
septicemia. In both typhoid fever and the septicemia the organism has moved out of the GI
tract and into the blood stream.
1. The onset of any Salmonella infection begins with the attachment and
internalization of Salmonella into the cells of the small intestine. If the
organism is then passed out of the mucosa cells into the underlying tissues the more
severe type of infection can result as the bacteria reach the blood stream and are widely
2. The death of the mucosa cells lead to loss of the ability of the colon to
concentrate the stool. Whether this death is due to the toxin produced by Salmonella or to
the response of the host's immune system is currently unclear.
3. The etiologic agent of typhoid fever is Salmonella typhi. It is
able to establish a carrier state in which the host sheds the organism for extended
periods of time (this was the case for Typhoid Mary). In this way food or water is
contaminated and the organism is passed on.
D. Infection with less virulent species of Salmonella can lead to a severe but
self limiting gastroenteritis referred to as salmonellosis. The bacteria
that cause this condition are routinely found in eggs and on poultry. Ingestion of
undercooked eggs or chicken or contamination of other foods with drippings from uncooked
infected meat can result in infection.
E. E. coli is a major component of the human gut flora. For the most part, this
organism is a harmless member of the gut community. Certain strains of E. coli are
able to produce proteins that are toxic or allow for attachment to certain types of
epithelium and invasion into the mucosa. These strains cause considerable morbidity.
1. Enterotoxigenic strains of Escherichia coli (ETEC)
are those that produce two enterotoxins heat-labile toxin (LT) and heat-stable
toxin (ST). The genes for these toxins are usually found on plasmids.
a. This LT-toxin is very similar to choleragen, the toxin produced by Vibrio
cholerae both in biochemical makeup and in mode of action. Thus E. coli strains
capable of producing these toxins cause diarrhea that is similar to that seen in cholera.
b. Contraction of virulent strains of E. coli by infants can result in infantile
diarrhea. This is a major cause of infant mortality.
c. Collectively, these strains of E. coli cause what is referred to as travelers
diarrhea. The local population becomes immune to those toxins produced by the
bacteria found in the water or food supply. The person who is not immune (the traveler) is
exposed to these toxins for the first time resulting in disease. Avoidance of drinking
water helps to reduce the chances of having this type of problem but remember that most
foods are prepared or washed with local water.
2. Enterohemorrhagic E. coli (EHEC) are strains of E. coli which
produce a toxin similar to that produced by Shigella organisms. Infection with
extremely small doses of EHEC can lead to disease. Often this organism is carried on meat
(hamburger, poultry) and is ingested if the meat is not properly cooked. The resulting
disease is similar to what is seen when a person is infected with Shigella.
3. Enteroinvasive strains have cell surface proteins that facilitate the
movement of the bacteria across the gut mucosa and allow it to disseminate systemically.
VI. Viral infection of the digestive tract is very common. Many, if not most, cases of
enteritis are due to viral infection of the mucosa cells. Some of the most common viral
pathogens are of a group of related viruses known as the enteroviruses.
These are small, non-enveloped viruses that multiply in the gut mucosa and are transmitted
from person to person by the fecal-oral route. They are spread throughout the body via the
blood stream. Most infections occur during childhood, and they are usually transient but
produce lifelong immunity. Clinical syndromes are generally mild, but occasional
infections may cause serious disease e.g. paralytic poliomyelitis, meningitis, or
myocarditis. The enteroviruses are of the family Picornaviridae (pico=SMALL - RNA
viruses). There is a high degree of serological cross reactivity between the 72 members of
the family Picornaviridae. Along with Poliovirus some of the more common enteroviruses
include Coxsackie A and B, Echovirus and several viruses which have received numerical
designation only as Enteroviruses 68-71.
VII. Hepatitis refers to any condition in which the liver becomes
inflamed. This may be the result of toxic ingestion, bacterial infection or other less
well defined etiologies. Viral hepatitis results from the invasion of liver
cells by viruses and the resulting cytopathology. Currently several viruses are known to
infect the liver causing viral hepatitis. They are referred to as hepatitis A,
hepatitis B, hepatitis C, hepatitis D (delta agent),
hepatitis E and hepatitis G. There are probably many other
viral agents that are currently circulating that have yet to be isolated and
characterized. We will concentrate on the hepatitis viruses that are transmitted via the
A. Hepatitis A virus (HAV) is often referred to as infectious
hepatitis. It is an RNA containing nonenveloped virus. It gains entry into the
body by fecally infected foods or water. Initial infection appears to be of cells lining
the GI tract. This initial infection results in diarrhea, vomiting, anorexia and mild
fever. It may gain entry to the underlying lacteals and blood vessels and spread to the
liver. This results in reduced liver function, jaundice and liver
tenderness. Recovery can take 4-6 weeks. There is a relatively low rate of mortality
1. As mentioned earlier, transmission is by the fecal-oral route. Infected individuals
will shed virus in their feces. Improper hand washing or sanitation can result in
transmission fairly readily.
2. Serological tests can be used to confirm exposure to HAV and shedding of viral
particles in the feces. Elevated liver enzymes (transaminases) also are
suggestive of viral hepatitis.
B. The disease caused by Hepatitis E virus (HEV) is called hepatitis E,
or enterically transmitted non-A non-B hepatitis (ET-NANBH). Other names include
fecal-oral non-A non-B hepatitis, and A-like non-A non-B hepatitis. The virus is an RNA
virus and is nonenveloped. Hepatitis caused by HEV is clinically indistinguishable from
hepatitis A disease. Symptoms include malaise, anorexia, abdominal pain, arthralgia, and
fever. Diagnosis of HEV is based on the epidemiological characteristics of the outbreak
and by exclusion of hepatitis A and B viruses by serological tests. HEV is transmitted via
the fecal-oral route. Waterborne and person-to-person spread have been documented. The
potential exists for food-borne transmission. Outbreaks of Hepatitis E occur in both
epidemic and sporadic-endemic forms, usually associated with contaminated drinking water.
Major waterborne epidemics have occurred in Asia and North and East Africa. To date no
U.S. outbreaks have been reported.
Here are some good links!
From the online medical microbiology text,
Foodborne Pathogenic Microorganisms and Natural Toxins