Heat-Killed Bacteria's Role in Inducing an Innate Immune Response and its Possible Link to Autism
By Linda Carlton and Mary Brauninger
Introduction
Autism, a childhood disorder whose behavioral symptoms usually manifest within the first few months of life, has been recently linked to environmental etiology. This paper presents the hypothesis that autism may be the result of a disease created by man due to the aberrant use of chemicals, drugs, vaccinations, environmental toxins and poor nutrition.
History and Today
The first known cases of autism seem to have appeared around the 1940s in America. There were several programs of change occurring during those years: the chlorination of water, the pasteurization of milk, and newly established immunizations to protect the health of the public, children and adults alike. (Marr and Malloy 1996)
All three of the above-mentioned programs were initiated for public safety in the control of bacterial and viral diseases. Thimerosal, found in many vaccines, is an organomercurial antiseptic that is anti-fungal and bacteriostatic for many nonsporulating bacteria and is used as a topical anti-infective or as a pharmaceutical preservative.
Other methods employed today to eliminate or control bacterial growth include low or high temperatures, chemicals, gases, microfiltration, bactofugation, sanitation and flavors. (Champagne et al 1994) Pasteurization is a process that stops fermentation in which the medium is brought to up to temperature levels sufficient enough to cease fermentation and kill bacteria. Vaccine programs also use this method of heat-killing bacteria and viruses to induce an immune response or tolerance to disease without infecting the subject.
It is commonly known that raw milk will sour, but pasteurized milk will putrefy. The idea that putrefaction of the stools causes disease (i.e. intestinal autointoxication) originated with physicians in ancient Egypt (Chen and Chen 1989). The toxic process, however, was reversed by the consumption of lactic acid-producing bacteria that changed the colonic microflora and prevented proteolysis (Chen and Chen 1989).
Autointoxication is an ancient theory based on the belief that intestinal waste products can poison the body and are a major contributor to many, if not all, diseases (Ernst 1997). By ancient tradition, lactic acid bacteria (LAB) are involved in the production of fermented foods. German scientists found that foods rich in LAB constitute one quarter of the German diet and are characterized by a safe history, certain beneficial health effects, and an extended shelf life when compared with raw materials (Hammes and Tichaczek 1994).
Microflora--'Early Life Studies'
In Finland, a double blind study revealed that when pregnant and lactating mothers and their babies were administered LAB, the immunoprotective potential of the mother's breast milk was increased (Rautava et al 2002). The study found that the amount of anti-inflammatory transforming growth factor beta2 (TGF-beta2) in the milk of mothers receiving LAB as compared to mothers receiving a placebo was significantly higher (Rautava et al 2002). Rautava documented that breast-fed babies, unlike bottle-fed babies, have a microbic intestinal flora characterized by a marked predominance of bifidobacteria and LAB (Coppa 2002).
A breast-fed, full-term baby has a preferred intestinal microbiota in which bifidobacteria predominate over potentially harmful bacteria, whereas, in formula-fed babies, coliforms, enterococci, and bacteroides predominate (Dai and Walker 1999). It is unlikely, however, that a lower ability to ferment carbohydrates is a major cause of increased risk of diarrhea in formula-fed babies, but individual short chain fatty acid (SCFA) production may be important (Parrett and Edwards 1997).
In essence, the formula-fed baby develops a much different microflora than that of a healthy, full-term, breast-fed baby.
Autism & Ammonia--'Behavioral Symptoms'
In 1989 Drukker documented the first case of a patient with autistic-like symptoms found to also have abnormal blood ammonia. Drukker reported that the subject had symptoms of dementia, amnesia, and cognitive disorders and reportedly 'misdiagnosed' as autistic.
Later in 2002, Cohen found that by an approximate one-third reduction of GABA and ammonia levels for an autistic patient, there was noticeable improvement of verbal/language skills and a reduction of repetitious, ritualistic, self-stimulatory behavior (stimming).
LAB, lactitol, and lactulose have all been clinically shown to reduce blood ammonia (Loguercio et al 1987, Vince and Burridge 1980). Ammonia is produced by intestinal-bacteria (Vince and Burridge 1980). The largest amount of ammonia is generated by gram-negative anaerobes, clostridia, enterobacteria, and Bacillus spp (Vince and Burridge 1980).
Gram-positive non-sporing anaerobes, streptococci, and micrococci formed modest amounts of ammonia while lactobacilli and yeast formed very little ammonia; therefore ammonia may be predominantly formed from bacterial cells in the colon (Vince and Burridge 1980).
Gluten & Casein
Laboratory studies have provided evidence that casein, gliadins, and glutenins are hydrolyzed or degraded by fermentation with LAB, providing better digestibility and cereal tolerance. Dietary lipids influence the gastrointestinal microbiota and, specifically, the population of LAB (Bomba et al 2002).
The favorable protein utilization and body mass increment on fermented milk diets are attributed to a better digestibility of proteins in these products (Vass et al 1984, Chebbi et al 1977). A great deal may depend upon the dough acidification or quality of specific LAB species, live or heat-killed during processing, whether bleached or unbleached flour is used, pasteurized or raw milk in the processing of consumer goods.
Several autism studies have hypothesized that the behavioral symptoms in autism may occur due to opiate-like activity. Opiates are sleep-inducing drugs, and opioids are naturally occurring peptides with similar effects. An example would be that of warm milk, which induces sleep through a natural release of peptides into the system.
In autism, there are characteristic symptoms of sleeping disorders. In fact, a review of the literature on the behavioral effects of opioid-like peptides failed to include any of the common characteristic symptoms described in autism. Children with autism have been documented to have increased urinary peptides (Whiteley and Shattock in 2002). These peptides are broken down either by host bacteria or natural fermentation. These specific peptides were derived from dietary sources, in particular foods containing gluten and casein that are known to produce opiate-like affects (Whiteley and Shattock 2002).
Studies preformed on the effects of beta-casomorphin-7 indicate they activate a histamine release in vitro in the presence of copper (II) (Lodyga-Chruscinska et al 2000). Skin tests with opioid peptides naturally occurring in cow's milk (such as beta-casomorphin-7 and alpha-casein) showed wheal and flare reactions similar to histamine and codeine that were observed in all children (Kurek et al 1995, Kurek et al 1992).
Beta-casomorphin-7 and alpha-casein are noncytotoxic histamine releasers in humans (Kurek et al 1992, 1995). The bioactivities of peptides encrypted in major milk proteins are latent until released and activated by enzymatic proteolysis, e.g. during gastrointestinal digestion or food processing (Meisel H, Bockelmann
1999).
The proteolytic system of LAB can contribute to the liberation of bioactive peptides (Meisel H, Bockelmann 1999). LAB were shown to liberate oligopeptides from beta- and alpha-caseins that contain amino acid sequences present in casomorphins, casokinines, and immunopeptides (Meisel H, Bockelmann 1999). The further degradation of these peptides by endopeptidases and exopeptidases of LAB could lead to the liberation of bioactive peptides in fermented milk products (Meisel H, Bockelmann 1999).
Autism Microflora
According to recent laboratory findings by Finegold in 2002, some cases of late onset (regressive) autism may involve abnormal flora. The fecal flora of children with regressive autism showed much higher clostridial counts than that of control children, not unlike those studies done on breast-fed and infant formula-fed babies (Finegold et al 2002). Finegold found a total absence of non-sporulating bacteria in the autistic children; in effect, thimerosal, by definition, targets such strains.
The more popular among diet choices recommended for autistic children is the casein-free and gluten-free diet. While an elimination diet may avoid the offending proteins, it also removes all dietary sources of LAB. Elimination diets (just as in infant formulas replacing mother's milk) have inherent gaps that create a need for supplementation of vitamins, minerals and amino acids; but it is also the absence of LAB that makes these diets problematic.
In 1983, Siegenthaler suggested that under certain conditions cultured milk, rather than fluid milk, can be used for infant formula and child nutrition as well as for school milk programs. Inappropriate handling of pasteurized milk is often responsible for a high bacterial count and organoleptic defects (Siegenthaler 1983).
The advantage of LAB fermented milk is the low pH created by the high lactic acid content that detrimentally affects food spoilage and pathogenic organisms in milk (Siegenthaler 1983) resulting in a longer shelf life of the fermented product at ambient temperatures (Siegenthaler 1983). Fermented milk products contain the enzyme lactase that facilitates digestion of residual lactose even after ingestion (Siegenthaler 1983).
Proinflammatory Cytokines
In 2001, Jyonouchi tested innate and adaptive immune responses in children with developmental regression and autism spectrum disorders. She found that children with autism produced higher levels of proinflammatory and counter-regulatory cytokines without stimuli than controls. Her results indicate excessive innate immune responses in a number of autistic children that may be most evident in TNF-alpha production. A fermented-milk, kefir, contains a substance that enhances IFN-beta secretion, the active substance that was identified to be sphingomyelin (Osada et al 1993-94).
The gastrointestinal system is continually subjected to foreign antigenic stimuli from food and microbes (Schley and Field 2002). Intestinal epithelial cells respond to lipopolysaccharides from gram-negative bacteria (Vidal et al 2002) and observations suggest that gram-positive organisms from lactic acid bacteria temper this reaction and prevent an exaggerated inflammatory response (Vidal et al 2002).
Summary
Sixty-plus years have passed, and autism still remains a mystery.
Through the efforts made by modern technology to control bacteria and disease, the destruction of non-pathogenic bacteria has disabled our ability to battle disease.
The attempt to artificially replace mother's milk has created a flawed and harmful bacterial ecosystem in our offspring. Many rural societies provide a diet that contains sufficient quantities of non-pathogenic bacteria. Dietary proteins are broken down through a process of fermentation with non-pathogenic bacteria.
A feasible solution would be to ferment foods as has been practiced for many centuries rather than elimination of casein and gluten. Scientific studies have found that the use of antibiotics were futile in the attempt to control harmful fecal bacteria; however, non-pathogenic bacteria has been clinically shown to be effective in studies done on other diseases with far worse conditions.
Autism is a behavioral disorder defined by characteristic symptoms that we must compare with other diseases or conditions to lead us to a stronger association. Heat-killed bacteria induce an innate immune response; however, only live bacteria can repair mucosal barriers to temper immune responses.
Linda Carlton is an independent researcher and mother of an autistic son. Mary Brauninger is an independent researcher and mother of five. Two are autistic.
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