Go With Your GUT.
The human cell is analogous to a complex industrial plant. It cannot operate properly with inadequate raw materials, malfunctioning metabolic machinery or in the presence of too many toxic compounds. It is critical our cells receive adequate nutrition, but how can our bodies benefit if nutrition is consumed but not delivered at the cellular level?
The gastrointestinal tract has three primary physiological functions: food digestion, nutrient absorption and eliminating toxins from the body. Failure of any one of these functions can lead to decreased energy production, increased energy needs and excess usage of body reserves, which serve as a buffer against the development of diseases.
For thousands of years, we have known nutrition is essential in maintaining good health. However, the role of the gastrointestinal tract as the site of origin and/or site of exacerbation of many diseases is a relatively new concept. About 100 years ago, Elie Metchnikoff conceived the notion that the development of many illnesses originated from a "toxic bowel." In his eagerness to cure, he went a little overboard by recommending a colectomy as treatment for many of his patients. Needless to say, this had limited success and the concept rapidly fell into disrepute. Nonetheless, Metchnikoff's concept stands as a major contribution in medical history.
Over the past 30 years, there has been renewed interest in the metabolic consequences resulting from disordered intestinal ecology (dysbiosis) and from increased intestinal permeability (leaky gut syndrome). These two concepts have revolutionized the way we look at the normal function and malfunction of the gastrointestinal tract, as well as the relationship between these concepts and the development of disease.
As we learn about dysbiosis and leaky gut syndrome, we discover they can exist separately or simultaneously and each can cause the development of the other. Additionally, they are particularly important because of their widespread presence in clinical situations. We will learn that the clinical management of dysbiosis and leaky gut syndrome is critical in controlling the manifestations of many underlying disease processes, as well as preventing potential diseases prior to the onset of clinical symptoms.
A complex ecological balance exists between the microflora in the gastrointestinal tract and its human host. When the host and microflora coexist in harmony, a healthy state of symbiosis results. When they live in dys-symbiosis (or "dysbiosis" for short), this disordered ecology often results in mal-homeostasis and--ultimately--clinical disease.
The gastrointestinal flora has been called 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.
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 K, [B.sub.5], [B.sub.6] and biotin, synthesis of short chain fatty acids (SCFA's) such as butyrate, crowding out of pathogenic flora, as well as the stimulation of the secretory immunoglobulin A antibody (SIgA) and intramural antibody systems.
The presence of abnormal microflora in the gastrointestinal tract can result in:
* deactivation of digestive enzymes that can lead to maldigestion and malnutrition consumption of vitamin [B.sub.12] and certain amino acids
* saturation of essential omega three and six fatty acids
* disruption of the intestinal lining, potentially causing leaky gut syndrome
* sensitization against translocated bacteria and their fragments that can lead to leaky gut syndrome and to autoimmune diseases
* development of yeast overgrowth syndromes
* development of irritable bowel syndrome and inflammatory bowel disease such as C. difficile enterocolitis
* deconjugation of bile acids and estrogen, potentially inducing bowel or breast cancer
The causes of dysbiosis are far more prevalent than generally recognized 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 microflora make up. The microflora by itself, however, is rarely the instigator of dysbiosis. What happens that enables certain amounts of organisms to overgrow, thereby upsetting the previously existing ecological balance? What makes an organism pathogenic when it's normally commensal?
There are two factors that determine the pathogenicity of an organism. First, the virulence of the organism or its ability to overgrow and produce toxins that can injure the human host. The second factor, host resistance, is half-heartedly acknowledged by modern medicine, but generally not addressed adequately. In fact, it is widely believed the organism invading the tissues is the primary underlying problem and 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. Yet, in other circumstances--such as when patients are immunocompromised in cases of AIDS or cancer--modern medicine pays more attention to the fact that host defenses are weakened. In these situations, rather than focusing on augmenting host defenses, the goal seems to be killing organisms that might be potential pathogens. Indeed, it is seen as a war between man and germs.
It should be clear that the presence of dysbiosis is, at the very least, an indication of something abnormal in the gastrointestinal tract that should be investigated. There are at least nine variables that can lead to dysbiosis:
2. Inflammatory conditions
7. Xenobiotic exposure
8. Immune dysfunction
9. Miscellaneous conditions
It should not be surprising 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. If we consume adequate amounts of fiber, these bacteria will flourish.
Diets high in fat and meat and low in fiber can lead to "putrefactive dysbiosis." In this situation, a potentially pathogenic bacterium called bacteroides tends to proliferate. Because they produce urease, the result is overproduction of ammonia.
In this setting, the pH of the stool becomes more alkaline, SCFA production of butyrate decreases and enzymes capable of deconjugating bile acids and estrogen are generated. These biochemical changes lead to nutritional shortages for colon and, to a lesser extent, small intestinal mucosal cells, as well as increased levels of bile acids (increasing the risk for colon cancer) and estrogen (possibly increasing the risk of breast cancer).
Inflammatory conditions of the intestinal tract such as Crohn's disease and a variety of infectious agents (bacterial, viral, fungal and parasitic) can cause mechanical disruption of the intestinal lining and subsequent loss of normal defense mechanisms that prevent the growth of many bacterial strains. A wide variety of opportunistic microorganisms can then take advantage of this environmental change and create an ecological shift in the microflora. The metabolic products of many of these 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 due to 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. 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, possibly resulting in maldigestion. This type of dysbiosis has been called "fermentation excess dysbiosis."
Stress can have profound effects on the psycho-neuro-endocrine-immune systems of the gastrointestinal tract that can lead to lowered host defenses.
In addition, the completion of the digestive process refers to the time it takes for food to pass through the intestinal tract (transmit time), which can be substantially altered by the neuroendocrine effects of stress.
The use or abuse of antibiotic drugs may be the single most frequent cause of dysbiosis. In every instance where antibiotics are used, profound changes occur in the consistency of the microflora in the gastrointestinal tract and possibly every other location of the body where there is a microflora (i.e. mouth, vagina, lungs, skin and conjunctiva). If host defenses are adequate and the resulting ecological balance is not too severely disturbed, the normal microflora may be able to reestablish its original health-promoting relationship.
However, in situations 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, potentially resulting in clinical disease. This condition, where the bowel microflora has been substantially reduced, is termed "deficiency dysbiosis." Deficiency dysbiosis can also develop as a result of inadequate fiber consumption, the major source of nutrition for the normal, health-promoting intestinal flora. One of the most dreaded iatrogenic diseases that often develops in this situation is clostridium difficile enterocolitis, a potentially life threatening "complication" of antibiotic usage.
Ironically, conventional medical treatment of this condition involves additional antibiotic therapy .timed 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 microorganisms invading the body without regard for the primary underlying ecology of the microflora or its human host's defense mechanisms.
I have treated a number of deficiency dysbiosis cases in which perplexed physicians have witnessed recurrences of enterocolitis despite multiple courses of progressively aggressive antibiotic therapy. A more rational approach is to prescribe low-dose antibiotic therapy for a few days, then simultaneously replace the friendly bacteria and fiber that pathogenic microorganisms require for subsistence. The next step would be to stimulate the growth and development of the intestinal tract's immune system and provide nutritional support that allows the gastrointestinal mucosal surface to repair itself.
In this age of widespread synthetic chemical production, our harmful environmental exposures are increasing at an alarming rate. 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 (e.g., toothpaste, mouth wash, dental amalgams, etc.). These substances damage the intestinal tract cells, thereby lowering host resistance to the microflora itself. A wide variety of pharmaceutical drugs such as steroids, birth control pills, NSAIDs, some chemotherapeutical agents, antacids, [H.sub.2] blockers, etc., can have profound effects on the balance of the gut microflora. Both of these factors can create an environment that favors changes in the ecological balance of the intestinal tract, thus setting the stage for the development of dysbiosis.
One of the best kept secrets in health care is that the gastrointestinal tract is the largest immune organ in the human body. It should not really come as much of a surprise, however. The intestinal lining has a huge surface area that separates the external world from the internal boby milieu. What location is strategically better for the body's defense system than at the entry site for potentially dangerous organisms or chemicals? If this large, appropriately placed immune system isn't working up to par, the lowered defenses that ensue may not be sufficient to keep the ecology of the intestinal tract in balance.
The immune system can malfunction in at least three ways. First, immunosuppression prevents an adequate response to fight off invaders, as seen in cases of extreme stress, cancer and AIDS. Second, it can become hyperresponsive to normal stimuli, as occurs in asthma, migraine or food allergies. This can result in not only the body's immune reserves being used up, but may cause immune reactions that injure normal tissue. Third, it can set the stage for autoimmune reactions, wherein antibodies are made against our own tissues, as in cases of 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 including 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 usually found in patients that are totally asymptomatic. Nonetheless, the presence of disordered intestinal ecology is clearly an abnormal situation and may serve as a warning of the imminent onset of clinical disease. Certainly, the presence of dysbiosis warrants a full laboratory evaluation of gastrointestinal function that includes at least an assessment of intestinal permeability and liver detoxification profile. Because the nine variables that can lead to dysbiosis relate to almost everyone, it is the author's opinion that a CDSA is a reasonable and cost-effective screening test that should be performed 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 imbalanced 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 removed. When managing dysbiosis, it is important to treat such an underlying cause whenever possible. This requires addressing each of the nine variables as possible cause factors and finding ways to eliminate them. The general approaches 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.
The microorganisms normally inhabiting a healthy gastrointestinal tract have been identified as acidophilus and E. Coli, mainly consisting of several species of bifidobacter. These organisms can be cultured, put into capsule form and adsorbed into the intestinal tract to reestablish a healthy ecological balance. These bacteria are termed "probiotics," meaning supporting the microflora. This contrasts antibiotics, which kill the microflora. A "prebiotic," which consists of the microflora's nutritional fiber the microflora must have as nutritional support to sustain continued growth, is often added to this mixture of probiotics.
As previously discussed, the health of the intestinal mucosal cells is important in maintaining host resistance, which is a powerful determinant in controlling which microflora will survive. Nutritional support for the intestinal mucosal cells is also 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 recommend 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, gamma orizanol, bioflavinoids like quercitin and antioxidants (coenzyme Q10, lipoic acid, glutathione and ginkgo biloba).
Host immunity is another important factor 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 states (as with food allergies or autoimmune conditions), levels of SIgA can be increased. Treatment of this problem 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 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. It is important to remember these factors are inextricably interwoven. Additional issues such as adequate rest, exercise, stress reduction and lifestyle purpose must all be considered when developing a healing strategy for each patient.
Len Saputo, M.D., is a board certified specialist in Internal Medicine with nearly 30 years of clinical experience. He is founder and director of the non-profit Health Medicine Forum, as well as the founder and CEO of the Health Broadcast Network, which operates the only Web site on the Internet (http://www.healthbroadcastnetwork.com) devoted to health that uses cybercasting (video) as its primary medium. For more information, contact Saputo at Len@heahhbroadcastnetwork.com or (925) 934-6165.