Health Medicine Center Article
|A Practical Clinical
Guide to Understanding
Dysbiosis and Irritable Bowel Syndrome (IBS)
|by Len Saputo,
The human cell is analogous to a complex industrial plant in that it
cannot operate properly without adequate raw materials, with
malfunctioning metabolic machinery, or in the presence of too many
toxic interfering compounds. Indeed, it is critical that our cells
receive perfect nutrition, but this benefit cannot be realized if
the nutrition consumed is not delivered to the cellular level.
gastrointestinal tract has three primary physiological functions:
digestion of food, absorption of nutrients into the body, and
keeping toxins out of the body. Failure of any of these functions
will lead to defective energy production, increased energy needs,
and wasting of the body’s reserves that serve as a buffer against
the development of disease.
That nutrition is
important in maintaining good health has been known for thousands of
years. However, the role of the gastrointestinal tract as the site
of origin and/or exacerbation of many diseases is a relatively new
concept. Elie Metchnikoff, about 100 years ago, conceived the notion
that the development of many illnesses originated from a “toxic
bowel.” In his eagerness to cure, he went a little overboard and
began to recommend a colectomy as treatment for many of his
patients. Needless to say, this had very limited success, and his
cure as well as his concept rapidly fell into disrepute.
Nonetheless, Metchnikoff’s concept stands as a major contribution in
Over the past 30
years there has been a renewed interest in the metabolic
consequences that can result from disordered intestinal ecology (dysbiosis)
and from increased intestinal permeability (leaky gut syndrome).
These two concepts have revolutionized the way that we can look at
the normal function and malfunction of the gastrointestinal tract,
as well as the interconnectedness of these concepts to many disease
We will discover,
as we learn about dysbiosis and leaky gut syndrome, that they can
exist separately or simultaneously, and that each can cause the
development of the other as well. Additionally, they are
particularly important because of their widespread presence in so
many clinical situations. We will learn that the clinical management
of dysbiosis and leaky gut syndrome is critically important in
controlling the manifestations of many underlying disease processes,
as well as in the potential prevention of diseases prior to the
onset of clinical symptoms.
Nature, when finally
understood, will reveal its remarkable balance and infinite wisdom.
This incredible perfection is exemplified par excellence in the
complex ecological balance that exists between the microflora in the
human gastrointestinal tract and its human host. When the host and
the microflora co exist in harmony, a healthy state of symbiosis
results. When they live in dys symbiosis, or for short, in “dysbiosis,”
this disordered ecology often results in mal-homeostasis, and
ultimately in clinical disease. (1)
gastrointestinal flora has been equated to an organ system within
itself. There are more than 500 different bacterial species, 99% of
which are anaerobic, that collectively comprise more metabolic
activity than any organ system in the human body. (2)
A wide variety of
important functions are normally provided by the microflora when the
ecology is undisturbed and healthy. These normal functions include
the metabolism of hormones, carcinogens, and xenobiotics, the
synthesis of vitamins such as vitamin K, B5, B6 and biotin, the
synthesis of short chain fatty acids (SCFA’s) such as butyrate, the
crowding out of pathogenic flora, as well as the stimulation of the
secretory immunoglobulin A antibody (SIgA) and intramural antibody
The presence of
abnormal microflora in the gastrointestinal tract can result in a)
deactivation of digestive enzymes that can lead to maldigestion and
malnutrition, b) consumption of vitamin B12 and certain amino acids
(6), c) saturation of the essential omega 3 and 6 fatty acids, d)
disruption of the intestinal lining that can cause the leaky gut
syndrome (7), e) sensitization against translocated bacteria and
their fragments that can lead to leaky gut syndrome and to
autoimmune diseases (8, 9), f) development of yeast overgrowth
syndromes (10), g) development of irritable bowel syndrome and
inflammatory bowel disease such as C. difficile enterocolitis (11),
h) and the deconjugation of bile acids and estrogens that might
potentially induce bowel or breast cancer.(12)
The causes of
dysbiosis (see table 1) are far more prevalent than generally
appreciated by most medical practitioners. Basically, any situation
that can alter the physical, chemical, or physiological integrity of
the gastrointestinal tract can result in changes in the make up of
the microflora. The microflora by itself, however, is rarely the
instigator of dysbiosis. What happens that enables certain of these
organisms to overgrow, and thereby upset the balanced ecological
environment that previously existed? What makes an organism that is
normally commensal, pathogenic?
There are two
factors that determine the pathogenicity of an organism. First, the
virulence of the organism, or its ability to overgrow and then to
produce toxins that are injurious to the human host, is an obvious
factor. The second factor, host resistance, is one that modern
medicine half heartedly acknowledges but generally does not
adequately address. In fact, what is widely believed is that the
organism that is invading the tissues is the primary underlying
problem, and that eradicating it is the solution. It is interesting
that all organisms inhabiting the intestinal tract (including
friendly bacteria such as acidophilus), under the right
circumstances can cause sepsis and death (13). Yet, at other times,
i.e. when patients are immunocompromised, as in the case of AIDS or
cancer, modern medicine does pay attention to the fact that host
defenses are weakened. In these situations, rather than focusing on
increasing host defenses, the goal seems to be being more aggressive
at killing all organisms that might be potential pathogens. Indeed,
it is looked at as a war between man and germs.
It should be
becoming clear that the presence of dysbiosis is, at the very least,
a signal that there is something abnormal going on in the
gastrointestinal tract, and that it should be investigated. There
are at least 9 pathways that can lead to dysbiosis. They include:
2. Inflammatory conditions
7. Xenobiotic exposures
8. Immune dysfunction
9. Miscellaneous conditions
It should not be a
surprise that what we eat can affect which organisms will have a
growth advantage in our intestinal tracts. The microflora has to eat
too, and each bacterial species has specific nutritional needs that,
if met, will allow it to enjoy accelerated growth. The normal,
friendly bacteria that inhabit the gut survive on high fiber diets
(15). If we consume adequate amounts of fiber, these bacteria will
have the nutrition they need to flourish.
Diets that are high
in fat and meat and low in fiber lead to what is termed
“putrefactive dysbiosis.” In this situation, a potentially
pathogenic bacterium called bacteroides tends to proliferate and,
because it produces urease, results in the overproduction of
ammonia. In this setting, the pH of the stool becomes more alkaline,
SCFA production of butyrate falls, and enzymes capable of
deconjugating bile acids and estrogen are generated. The
consequences of these biochemical changes lead to nutritional
shortages for colon and, to a lesser extent, small intestinal
mucosal cells, as well as in increased levels of bile acids
(increasing risks for colon cancer) and of estrogen (possibly
increasing the risks for breast cancer).
conditions of the intestinal tract such as Crohn’s disease, and a
variety of infectious agents (bacterial, viral, fungal, parasitic)
can cause mechanical disruption of the intestinal lining, and
subsequent loss of normal defense mechanisms that prevent the growth
of many bacterial strains. Wide varieties of opportunistic
microorganisms can then take advantage of this change in environment
and create an ecological shift of the microflora. The metabolic
products of many of this new microflora are toxic to the bowel, and
cause further pathological changes; thereby creating a vicious cycle
that may be self-perpetuating.
Failure to digest
food because of insufficient gastric acid, lactase, or other
digestive enzymes, allows more nutrients to reach the lower small
intestine and colon, where the microflora can then overgrow (16-18).
This bacterial overgrowth can lead to the overproduction of enzymes
(proteases) that are able to degrade enzymes produced by the
intestinal lining and the pancreas, and can result in maldigestion.
This type of dysbiosis has been called “fermentation excess
Stress can have
profound effects on the psycho neuro endocrine immune systems of the
gastrointestinal tract that can lead to lowered host defenses
(19-21). In addition, the completeness of the digestive process is
related to the time it takes food to pass through the intestinal
tract (transit time), and this can be substantially altered by the
neuroendocrine effects of stress. These factors enable opportunistic
microorganisms to shift the ecological balance of the intestinal
The use and abuse
of antibiotic therapy may be the single most frequent cause of
significant dysbiosis in clinical practice today. In every instance
when antibiotics are used, there are profound changes in the
consistency of the microflora in the gastrointestinal tract, and
possibly in every other location of the body where there is a
microflora (i.e. mouth, vagina, lung, skin, and conjunctiva). If
host defenses are adequate, and the resulting ecological balance not
too deeply disturbed, the normal microflora may be able to re
establish it’s original health promoting symbiotic relationship.
However, in the
situation where there is repeated or prolonged antibiotic treatment,
especially in the presence of inadequate host defenses, a state of
severe and sustained dysbiosis may develop, which can then result in
clinical disease. This condition, wherein the bowel microflora has
been substantially reduced, has been termed "deficiency dysbiosis."
Another mechanism allowing deficiency dysbiosis to develop is the
inadequate consumption of fiber, the major source of nutrition of
the normal, health promoting, and intestinal flora. One of the most
dreaded iatrogenic diseases that too often develops in this
situation, is clostridium difficile enterocolitis, a potentially
life threatening “complication” of antibiotic usage.
It is ironic that
conventional medical treatment of this condition is to use
additional antibiotic therapy aimed at stopping the clostridium
difficile overgrowth. While this approach may be successful at
times, it demonstrates the typical, “us against the germs” attitude
of modern medicine. This approach focuses on killing the micro
organisms that are invading the body, without regard for the primary
underlying process that relates to the ecology of the microflora or
its human host’s defense mechanisms.
I have treated a
number of cases of this kind of deficiency dysbiosis, where
perplexed physicians have witnessed multiple recurrences of
enterocolitis despite multiple courses of progressively more
aggressive antibiotic therapy. A more rational approach is to give a
very short pulse of antibiotic therapy for a few days, and then
simultaneously replace the friendly bacteria and the fiber that they
require for sustenance, stimulate the growth and development of the
immune system of the intestinal tract, and provide nutritional
support that allows the gastrointestinal mucosal surface to repair
itself. To the surprise of most physicians with whom I have worked,
this approach has worked within a few days in every case I have
managed so far.
exposures are increasing at an alarming rate in this age of
widespread synthetic chemical production. Many of these toxic
substances find their way into the intestinal tract through food,
water and a variety of products that get into our mouths (i.e.
toothpastes, mouth washes, dental amalgams etc.). These substances
cause both damage to the cells of the intestinal tract, thereby
lowering host resistance, and to the microflora itself. Both of
these factors can create an environment that favors changes in the
ecological balance of the intestinal tract and sets the stage for
the development of dysbiosis. A wide variety of pharmaceutical
drugs, such as steroids, birth control pills, NSAIDs, some
chemotherapeutical agents, antacids, and H2 blockers etc. etc., can
have profound effects on the balance of the gut microflora (22).
One of the
best-kept secrets in health care is that the gastrointestinal tract
is the largest immune organ in the human body. When you think about
this, however, it should not really come as much of a surprise. The
intestinal lining has a huge surface area that separates the outer
external world from the internal milieu of the body. Where is there
a better strategic location for the body's defense system than at
the site of entry of potential dangerous organisms or chemicals? It
doesn't require a rocket scientist to envision that if this large,
strategically placed immune system isn’t working up to par, that the
lowered defenses that ensue may not be sufficient to keep the
ecology of the intestinal tract in balance.
Our immune systems
can malfunction in at least three ways. First, it can be weakened so
that it cannot mount up an adequate response (immunosuppression) to
fight off usual stresses as is seen in stress, cancer and AIDS.
Second, it can overreact in a way where it hyper-responsive to
normal stimuli, as occurs in asthma, migraine, or food allergies.
This can result in not only using up the immune reserves of the
body, but may cause immune reactions that create tissue injury.
Third, it can set the stage for autoimmune reactions, wherein
antibodies are made against our own tissues such as occurs in
rheumatoid arthritis or lupus. Regardless of the mechanism of immune
malfunction, the end result is the same, abnormal host defense
mechanisms that can lead to the development of dysbiosis.
The diagnosis of
dysbiosis centers around three approaches: a careful history and
physical examination, a comprehensive diagnostic stool analysis (CDSA),
and possibly, breath testing. It is also important to keep in mind
that dysbiosis is not a disease per se. As a matter of fact,
dysbiosis is usually found in patients that are totally
asymptomatic. Nonetheless, the presence of disordered intestinal
ecology is clearly an abnormal situation, and may be an important
finding that serves as a warning that the onset of clinical disease
is imminent. Certainly, the presence of dysbiosis warrants a full
laboratory evaluation of gastrointestinal function that includes at
least an assessment of intestinal permeability and a liver
detoxification profile (see the next section on leaky gut syndrome).
Because of the fact that the 9 pathways that can lead to dysbiosis
relate to almost everyone, it is the opinion of the author that a
CDSA is a very reasonable and cost effective screening test that
should be done on nearly every patient.
The degree of
difficulty in treating dysbiosis depends on host defenses and
nutritional status, as well as the severity of the disordered
ecology. In situations where there is a severe underlying disease
such as AIDS, cancer, or malnutrition, the dysbiosis may be
impossible to fully correct and may be only partially improved. In
the management of dysbiosis it is important to treat the underlying
cause whenever possible. This requires accessing each of the 9
pathways as possible factors that may be causing the dysbiosis, and
then finding ways to eliminate them. The general approaches that are
important in managing dysbiosis are aimed at restoring the normal
microflora, providing optimal nutrition for the intestinal mucosa,
reducing toxic environmental exposures, and restoring the intestinal
immune system’s SIgA antibody production.
normally inhabiting the healthy gastrointestinal tract have been
identified, and consist mainly of several species of bifidobacter,
acidophilus, and E. coli. These organisms can be cultured, put into
capsule form, and ingested into the intestinal tract, where they can
re establish a healthy ecological balance. These bacteria are termed
“probiotics,” meaning supporting the microflora, in contrast to
antibiotics, which kill the microflora. To this mixture of
probiotics is often added a “prebiotic,” which consists of the fiber
that the microflora must have as nutritional support to sustain its
As we have already discussed, the state of health of the intestinal
mucosal cells is important in maintaining host resistance, and host
resistance is a powerful determinant that controls which microflora
can survive. It is easy to understand that nutritional support for
the intestinal mucosal cells is necessary to maintain effective host
defense mechanisms. It is just as easy to appreciate the importance
of avoiding toxic exposures that could interfere with cellular
metabolism. Generally, I have recommended that patients consume
organic food, juice whenever possible, and use a variety of vitamins
(A, B's, E, and C, often to bowel tolerance), minerals, nutrients
(especially L glutamine and phosphatidyl choline), essential fatty
acids, gammaoryzanol, bioflavonoids like quercetin, and antioxidants
(coenzyme Q 10, lipoic acid, glutathione, ginkgo biloba). (23-32)
Host immunity is
another factor that is important in regulating the consistency of
the microflora. Secretory IgA levels in the intestinal lumen are
frequently either suppressed or exaggerated in dysbiosis. In
hyperimmune states, as in certain parasitic infections, or in
allergically mediated diseases, as with food allergies or autoimmune
states, levels of SIgA can be increased. Treatment of this condition
is accomplished by correcting the underlying condition. In
situations, where the SIgA is depressed, it can often be stimulated
through the use of saccharomyces boulardii or licorice root extract.
We must remember
that we are not just treating the gut, but a human being. This
always requires looking at the whole person and addressing issues
related to body, mind, and spirit, and remembering that these
factors are inextricably interwoven. Additional issues, such as
adequate rest, exercise, stress reduction, and meaningful purpose in
life, must all be considered when developing a healing strategy for
interrelationship of dysbiosis and leaky gut and the fundamental
importance in intestinal permeability will be presented in Part II
of this series on the function of the gastrointestinal tract in
health and disease.
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