Biological Treatments for Autism and PDD Online > Chapter 2: Part I | Part II
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The microorganisms in the gastrointestinal tract
by William Shaw Ph.D.
Bacteria in the intestinal tract
In order to understand how the widespread use of antibiotics may have such devastating effects, it is necessary to understand the role of microorganisms in the intestinal tract.
There are two main kinds of bacteria in the intestinal tract: aerobic and anaerobic. The aerobic bacteria need oxygen while the anaerobic bacteria don't need oxygen to live and even may be killed if oxygen is present. Some bacteria grow faster with oxygen but can adapt to a low oxygen environment. Another major group of organisms in the intestine are the yeast and fungi. In the intestinal tracts of some individuals there may be single-celled animals called protozoa as well. These organisms in a normal intestinal tract are found in a natural balance that is healthy. It is estimated that there are 500 or more different species of bacteria in the average human intestinal tract (1). Because there is not much oxygen in the intestinal tract, the anaerobic bacteria that don't need oxygen predominate. Of the 500 species, there are perhaps 30 or 40 species that constitute the majority of the bacteria present. It's estimated that there are about 10-100 trillion cells of bacteria in the intestinal tract at any one time (1). To give you an idea of the size of that number, there are about a 100 trillion human cells in the entire human body. Thus, 10-50 % of your total cells are due to bacteria in a normal individual who is not on antibiotics.
There are very few bacteria in the stomach because the stomach acid kills them. But, in the colon there are tremendous numbers: about a million times more in the colon compared to the stomach. The stomach acid kills most bacteria but the stomach acid is neutralized with bicarbonate from the pancreas in the normal individual as food passes into the small intestine. Bacteria constitute about 50% of the content of feces. These residents of the intestinal tract are always in a state of flux : new bacteria are continuously being produced and old bacteria are continuously being flushed out in the moving intestinal contents and later as feces.
In a study that was reported in the Journal of Infection and Immunology (2), it was found oral penicillin administered to experimental animals reduced the total population of anaerobic bacteria by a factor of 1,000 including beneficial bacteria which are called Lactobacilli. These bacteria are present in yogurt. As the good bacteria are killed off, the potentially harmful bacteria increase rapidly. This study reported translocation of the harmful bacteria out of the intestinal tract and into the lymph nodes surrounding the intestinal tract. From these lymph nodes, these bacteria were then strategically placed to cause new infections throughout the body.
Yeast overgrowth of the intestinal tract
Another harmful effect of antibiotics is that killing off all the normal bacteria results in the proliferation of yeast. There are hundreds of articles in the scientific and medical literature indicating yeast over-growth is associated with antibiotic use. Some of the most important are included in the references at the end of this chapter (3-13). There are two reasons for it. First, when the normal bacteria in the intestine are killed off, the yeast have no competition so they are able to get the lion's share of all the food that passes through the intestinal tract after a meal. Second, the yeast may actually be stimulated by many of the antibiotics (12,13).
Scientific work on animals is relevant to yeast infection in humans. Infant mice were much more susceptible to Candida infection than older mice and, once exposed to Candida at an early age, developed persistent candidiasis (3). If these mice were given antibiotics at an early age, the Candida in the intestinal tract increased an average 130-fold. Exposure of infant mice to the hormone cortisone increased Candida in the intestine 8-fold. Similar results are found in humans (5-11). Largely because of the overuse of antibiotics, the incidence of disseminated candidiasis has changed from a rare occurrence prior to 1960 to the fifth most common organism encountered in infections acquired at a hospital in Southern California (14). The reason these bacteria and yeast are important is because they produce chemical byproducts that are normally only present in very low concentrations. When yeast and bacteria, normally present in small quantities, reach extremely high numbers, they produce these byproducts in much higher concentrations. These byproducts of yeast and bacteria are then absorbed from the intestinal tract into the blood. From there, they circulate throughout the body to all the tissues and are eventually filtered out of the body into the urine.
In addition to the production of these byproducts, the yeast cells may convert to their more invasive colony form. The yeast in this hypha form imbed themselves into the lining of the intestinal tract like ivy climbing a brick wall. This attachment is facilitated by the secretion of yeast digestive enzymes at the point of attachment. The intestinal lining is thus digested by a variety of yeast enzymes including phospholipase A2, catalase, acid and alkaline phosphatases, coagulase, keratinase, and secretory aspartate protease (15-17). The secretory aspartate protease is of especial importance; it may destroy the lining of the intestinal tract and may also digest the IgA and IgM antibodies produced by the body to attack the yeast (15). The destruction of this gastrointestinal lining may be the reason for the abnormal secretin response discussed in the chapter on the digestive system.
Some of the intestinal cells probably die as a result of this attack. As a result of multiple yeast attaching to the intestinal lining, the lining may appear like Swiss-cheese on a microscopic level. Ordinarily, undigested food molecules would not be able to pass through this intestinal lining. However, because of the holes in the intestinal lining, undigested food molecules pass through. This phenomenon is called the leaky gut syndrome. A major consequence of the leaky gut syndrome is much greater susceptibility to food allergies. The undigested food is recognized as an invader by the immune system and as a consequence, antibodies of both the IgE and IgG types may start to be produced. After a while both behavioral and allergic reactions may occur after eating these foods. Many times patients with multiple allergies will be retested after antiyeast therapy and find that their allergies have disappeared. When the yeast overgrowth has been eliminated, the intestinal lining heals, the intestine is no longer leaky, and the immune system diminishes its attacks against the offending foods. If your child has multiple food allergies in addition to milk and wheat sensitivity, you may find it nearly impossible to implement a suitable diet. Therefore, I usually recommend that an underlying yeast problem always be treated at least 60 days before allergy testing is done.
Evidence for abnormal bacterial byproducts in autism
One of the chemical compounds in urine that I initially suspected was due to a yeast overgrowth of the intestine is called dihydroxyphenylpropionic acid-like compound (DHPPA). Several years ago, I began a collaborative study with Dr. Walter Gattaz, a research psychiatrist at the Central Mental Health Institute of Germany in Mannheim to evaluate urine samples of patients with schizophrenia. These samples were very valuable since they were obtained from patients who were drug-free. Thus, any biochemical abnormalities would be due to their disease and not a drug effect. Five of the twelve samples contained a very high concentration of a compound identified by GC/MS as a derivative of the amino acid tyrosine which is very similar to but is not identical to 3,4-dihydroxyphenylpropionic acid. I have termed this compound dihydroxyphenylpropionic acid-like compound (DHPPA-like compound). This compound is an isomer of dihydroxyphenylpropionic acid but I have not yet identified the exact isomer.
Newborns infants tested at approximately one month of age had extremely low values of this compound in urine since newborns are not colonized with intestinal germs. In older children, the values are much higher. In children with autism, values may be extremely high. There is some degree of overlap in the normal and autism population but the median and the mean values are significantly higher in the children with autism. (The median is the middle value of a group of numbers while the mean is the average value of the group.) The mean value for all infants is 3.7 mmol/mol creatinine with a standard deviation of 3.6 mmol/mol creatinine and a range from 0.3 - 12.7 mmol/mol creatinine. In normal male control children, the mean value is 91.5 mmol/mol creatinine with a standard deviation of 90.4; the median value in this group is 51.1 mmol/mol creatinine. In autistic male children, the mean value is double that of the controls: 192.4 mmol/mol creatinine with a standard deviation of 90.4; the median value in this group is 143.5 mmol/mol creatinine, nearly triple the value of the control group. In normal female control children, the mean value is 85.5 mmol/mol creatinine with a standard deviation of 55.9; the median value in this group is 74.5 mmol/mol creatinine. In autistic female children, the mean value is double that of the controls: 182.4 mmol/mol creatinine with a standard deviation of 200.6; the median value in this group is 111 mmol/mol creatinine, a value 49% greater than the control females. In all groups the median values are smaller than the corresponding mean values indicating that the values are not normally distributed and that the populations are skewed by some samples with very high concentrations of dihydroxyphenylpropionic acid-like compound.
What was surprising to me was that there was not a significant decrease in DHPPA-like compound after antifungal drug therapy. The mean value for the DHPPA-like compound actually increased a little. This increase indicated to me that this compound could not be due to the yeast but was probably due to a different microorganism Since several children and adults with Clostridium difficile infection of the intestinal tract had high values of DHPPA-like compound in their urine and the production of a similar compound, monohydroxyphenylpropionic is characteristic of different species of Clostridia(18,19), I suspected that one or more species of the bacteria genus Clostridium were producing this compound.
Some of the common species of Clostridium are Clostridium tetani that causes tetanus, Clostridium botulinum that causes the food poisoning botulism, and Clostridium perfringens and Clostridium difficile that cause diarrhea(20). Clostridium perfringens, Clostridium novyi, Clostridium bifermentans, Clostridium histolyticum, Clostridium septicum, and Clostridium fallax may all cause gangrene (20). Many other species of Clostridium are normal inhabitants of the intestinal tract but may not even be scientifically described and are not even named as a species. The major reason for a lack of knowledge about these organisms is that they are strict anaerobes that cannot tolerate oxygen. Since they must be processed in an oxygen free environment, many hospital laboratories do not have the capability to identify these organisms. The exception is Clostridium difficile which is identified by the toxin it produces in the stool rather than by the isolation of the organism itself. Clostridium difficile overgrowth of the intestinal tract causes a severe potentially fatal disorder called pseudomembranous colitis (21). This overgrowth is frequently associated with the use of oral antibiotics, indicating that this organism is resistant to many of the common antibiotics such as penicillin, ampicillin, tetracyclines, cephalosporins, chloramphenicol, and others (22). This organism is usually treated with either metronidazole (Flagyl) or vancomycin followed by a replenishment of the intestine with Lactobacillus acidophilus (23). Since many bacteria can genetically transfer drug resistance to other similar species and even unrelated species, it seems likely (to me) that multiple species of Clostridia may now be resistant to the most common drugs.
Another reason that I was interested in this compound was due to the theory of Ellen Bolte (Autism and Clostridium tetani: a hypothesis, Medical Hypotheses, In Press) that the tetanus bacteria (Clostridium tetani) might be responsible for some cases of autism. Her child developed autism after a DPT immunization which is a multiple immunization (Diphtheria, pertussis,and tetanus) which includes a tetanus toxoid. She was concerned that her child may actually have contracted tetanus from a contaminated vaccine. When the antibodies to tetanus were checked several years after this vaccination, the antibodies to tetanus were very high. Her child was extremely developmentally delayed and also had a high value of DHPPA-like compound in the urine.
There are some interesting parallels between autism and tetanus. Individuals with tetanus have extreme sensory sensitivity and may need to be placed in dimly lighted rooms (24,25). Loud noises had to be avoided. In addition, patients with this disorder might have difficulty chewing and swallowing; lockjaw is the other name for tetanus. Thus, Ellen's idea was that perhaps her child had a "subacute" tetanus that caused many of the symptoms of autism related to sensory sensitivity but would not be lethal because her child was immunized. Such cases of subacute tetanus have been reported even in individuals who had been immunized and had high levels of antibodies to the tetanus toxin (24,25). Although I thought it was highly unlikely that her child contracted tetanus from the vaccine, I thought it possible that he might have a Clostridium tetani overgrowth of the intestinal tract or an overgrowth of another species of Clostridium that might also be producing toxins similar to that of tetanus that might have caused the high antibody levels in her child. Clostridium tetani overgrowth of the intestinal tract has been demonstrated in rats (26). The toxins produced by several different species of Clostridia (tetani, botulinum, barati, and butyricum) are very similar biochemically (27) and therefore antibodies produced against one Clostridium toxin would also probably react against the tetanus toxin. Also the gene for the tetanus neurotoxin is located on a plasmid (28), a piece of "naked" DNA that can be easily passed on to different species of Clostridia and perhaps even other species of bacteria and which would confer on the new species the ability to make tetanus toxin. (Continue to Part II.)
Buy The newest version (2002) of this book online!
Biological Treatments for Autism and PDD Online > Chapter 2: Part I | Part II