Jag har många gånger skrivit om läckande tarm, då det är den åkomma som jag stöter på dagligen i mitt arbete med kost och hälsa. Nya rön som ser ljuset, påvisar den negativa påverkan på tarmens slemhinna, som påverkas av socker, vete, tillsatser m.m.
De låga PH-värden som en söt och sur kosthållning medför ger liknande effekt som en försurad sjö som växer igen och tappar livet. Detta innebär att ett lågt PH-värde behövas basas upp. Läs mer i tidigare inlägg: blog.php?bid=633&print=1
Socker och vete har en indirekt skadlig effekt på tarmväggen. Detta genom att de fungerar som näring för tillväxt av skadliga former av jästsvampar (exempelvis candida), vilka sätter sig fast i tarmens slemhinna. Detta kan skada den (göra hål) och därmed ge läckande tarm och ökad risk för allergier. Eftersom 80 % av immunförsvarets celler finns nere i tarmregionen, så är detta inte alls bra för immunförsvaret.
Det är dessutom vetenskapligt bevisat att glutenpeptider öppnar s.k. tight junctions i tarmväggen, varvid större partiklar kan passera och kraftigt reta immunförsvaret. (Källa: Sanna Ehdin)
Läs gärna denna artikel om du är intresserad:
Reprinted from AIA Newsletter No.18 (Summer 1997)
The purpose of the gastro-intestinal (GI) tract, or gut, is multi-fold. Basically, it:
i) Digests foods,
ii) Absorbs small food particles to be converted into energy.
iii) Carries nutrients like vitamins and minerals attached to carrier proteins across the gut lining into the bloodstream.
iv) Contains a major part of the chemical detoxification system of the body, and
v) Contains immunoglobulins or antibodies that act as the first line of defence against infection.
Leaky gut syndrome (LGS) is a poorly recognised but extremely common problem. It is rarely tested for. Essentially, it represents a hyper-permeable intestinal lining. In other words, spaces develop between the cells of the gut wall, and bacteria, toxins and food leak through. The official definition is an increase in permeability of the intestinal mucosa to luminal macromolecules, antigens and toxins associated with inflammatory degenerative and/or atrophic mucosal damage.
The Mucosal Barrier
The barrier posed by the intestinal mucosa is, even in normal subjects, an incomplete one. Small quantities of molecules of different sizes and characteristics cross the intact epithelium by both active and passive mechanisms. The route by which such transfer occurs is, at least in part, dependent on molecular size. Molecules up to about 5000 Daltons in size cross the epithelial membrane of the microvilli. Larger molecules may utilise an intercellular pathway or depend on being taken up by endocytosis entering the cell at the base of the microvilli.
How Does The Gut Become Leaky?
Once the gut lining becomes inflamed or damaged, this disrupts the functioning of the system. The spaces open up and allow large food antigens, for example, to be absorbed into the body. Normally the body sees only tiny food antigens. When it sees these new, larger ones, they are foreign to the body’s defence system. So the attack results in the production of antibodies against once harmless, innocuous foods.
Isn’t Leakier Better?
It might sound good that the gut can become leaky, because it would seem that the body would be better able to absorb more amino acids, essential fatty acids, minerals and vitamins. For the body to absorb a mineral it does not just slowly diffuse across the gut membrane it must be attached to a carrier protein. This protein hooks onto the mineral and actually carries it across the gut wall into the bloodstream. However, when the intestinal lining is damaged through inflammation these carrier proteins get damaged as well, so now the victim is vulnerable to developing mineral and vitamin deficiencies.
The 7 stages of the ’inflamed gut.
1 . When the gut is inflamed, it does not absorb nutrients and foods properly and so fatigue and bloating can occur.
2. As mentioned previously, when large food particles are absorbed there is the creation of food allergies and new symptoms.
3. When the gut is inflamed the carrier proteins are damaged so nutrient deficiencies can occur.
4. Likewise when the detoxification pathways that line the gut are compromised, chemical sensitivity can arise. Furthermore the leakage of toxins overburdens the liver so that the body is less able to handle everyday chemicals.
5. When the gut lining is inflamed the protective coating of lgA (immunoglobulin A) is adversely affected and the body is not able to ward off protozoa, bacteria, viruses and yeasts.
6. When the intestinal lining is inflamed, bacteria and yeasts are able to trans-locate. This means that they are able to pass from the gut lumen or cavity, into the bloodstream and set up infection anywhere else in the body.
7. The worst symptom is the formation of antibodies. Sometimes these leak across and look similar to antigens on our own tissues. Consequently, when an antibody is made to attack it, it also attacks our tissue. This is probably how autoimmune disease start.
Abnormal intestinal permeability in PDD | GI symptoms associated with PDD |
Gluten and gut permeability | Tight junctions and gut permeability
Reproduced by kind permission of Prof. Glenn Gibson, University of Reading, UK.
Autism and the Human Gut Flora
Dr. Max Bingham
Food Microbial Sciences Unit, Science and Technology Centre, Earley Gate, University of Reading,
Whiteknights Road, Reading, Berkshire, UK. RG6 6BZ
Previous research into autism has raised the possibility that a link exists between the disorder and the human gut microflora. Research has remained limited due to the unwillingness of the orthodox medical establishment to adopt treatments suggested by this research. This short review aims to summarise the research completed to date and evaluate the relevance of a link between autism and a possible imbalance in the human gut microflora. It appears that yeasts (Candida species in particular) and clostridia may play an important role in the development of autistic symptoms. It is suggested that the control of the growth of these species may reduce the severity of autistic symptoms but is unlikely to offer a cure.
Previous research into autism has raised the possibility that a link exists between the disorder and the human gut microflora. However the relevance of this to sufferers of Autism has remained somewhat un-researched. As a consequence, it appears that the treatments suggested previously have remained unused and regarded by the orthodox medical establishment as irrelevant. This short review will consider the limited research completed to date.
The term autism is usually associated with the syndrome first described by Kanner (1943). In more recent years specific criteria have been set out to aid in the diagnosis of the disorder (Shaw et al, 1999). Autism typically develops early in childhood however causality, explanation and treatment are often hotly debated. Symptoms can include (but not necessarily), hyperactivity, loss of eye contact, decreased vocalisation (i.e. loss of language), stereotypical behaviours, poor academic performance and other similar social deficits. Other similar disorders exist. These include Asperger Syndrome, Attention Deficit Hyperactivity Disorder (ADHD), Pervasive developmental disorder (PDD) and many others, where symptoms are similar to Autism but specific differences are demonstrated.
Yeast metabolites in the Urine of Autistic Children
Yeasts constitute only a very small proportion of the population of the gut (Holzapfel et al, 1998) under normal conditions possibly kept from growing via competition from bacterial species and certain immune functions. However, Shaw et al (1999) has proposed that Autism (or at least many of the symptoms) may be a consequence of an overgrowth of candida species and a selective IgA deficiency. Following treatment with antifungal drugs and a gluten and casein free diet, a child rated as having severe autism improved such an amount as to be classed as a higher functioning individual with autism.*
It has been shown previously that children exhibiting autistic features have increased excretion of arabinose and the analogs of Krebs Cycle metabolites (including tartaric acid) (Shaw, Kassen & Chaves, 1995). Using Gas Chromatography/Mass Spectrometry (GC/MS) to test for urinary metabolites, it was found that the children had extremely high values of tartaric acid. The only source of tartaric acid is yeast (Shaw, 1999). Many reports have suggested that the onset of autism may be related to the occurrence in children of otitis media (Kontstantareas & Homatidis, 1987). It is common to treat otitis media with some sort of broad-spectrum antibiotic. Intestinal overgrowth of yeast and certain anaerobic bacteria are a well documented outcome of the administration of broad spectrum antibiotics (Kennedy & Volz, 1983; Danna et al, 1991; Ostfield et al, 1977; Kinsman et al, 1989; Van der Waaij, 1987; Samsonis et al, 1993, 1994a,b).
To evaluate this, it is known that Shaw (1999, 1996) has used GC/MS to test the urinary content of metabolites following the administration of Nystatin, an antifungal drug. Accordingly it was found that urinary tartaric acid declined to zero after about 60 days. When the Nystatin dose was cut to half, levels appeared to rise. Associated with this was seen an improvement in eye contact, a reduction in hyperactivity and an improvement in sleep patterns. It is unclear as to the method used, however these are interesting results. In other work, Shaw (1999) has evaluated the progress of the Herxheimer reaction of yeast die off. Values for the microbial metabolites described above increased dramatically during the first three days and began to normalise near day four. It is unclear as to the relevance of the point that many children take antibiotics for a whole series of illnesses, but do not develop autism.
Gupta et al (1996) have studied some possible modulating factors in Autism. These include immuno-deficiencies and probable differences in biochemical detoxification factors which appear to be very common in autism. It has been estimated that a high percentage of autistic children have a significant immune dysfunction that may include myeloperoxidase deficiency, a genetic deficiency that impairs the action of white blood cells on yeast cells, IgA deficiency, complement C4b deficiency, IgG deficiency or IgG subclass deficiency (Gupta et al, 1996). In the above study, a complete remission of autistic symptoms was achieved by infusions of gamma globulin in one case. Shaw (1999) has suggested that it seems increasingly likely that the immune system takes an inventory of bacteria and yeast cells present in the gut soon after birth. This inventory is performed by CD5+ B-cells. These cells may play a role in regulating the secretion of IgA, the antibody class that is secreted into the intestinal tract and which may select which micro-organisms are tolerated in the gut. Continuing, it is suggested that the eradication of the normal gut flora when antibiotics are administered repeatedly during infancy may cause the CD5+ cells to reject normal cells and award immune tolerance to species that potentially could cause harm. Either antibiotic use in infancy or yeast infection of the mother during pregnancy may result in later tolerance to yeast. This would possibly extend any remission from symptoms induced by methods of treatment suggested for autism.
Yeast and Tartaric Acid Toxicity
Shaw, Kassen & Chaves (1995) noted in their initial study of the two brothers with autism, that in addition to their autistic characteristics, they exhibited severe muscle weakness. Both of these brothers excreted large amounts of tartaric acid in their urine. It is known that tartaric acid is an analog of malic acid. Malic acid is a key intermediate in the Krebs cycle which is responsible for the extraction of most of the energy from food substrates. Tartaric acid is presumably seen as toxic since it would inhibit this pathway and limit energy production. This may be the reason for the muscle weakness seen in the two autistic brothers. It has also been shown that Candida albicans produce gliotoxins (Shah and Larsen, 1991 and 1992) and immunotoxins (Podzorski et al, 1989; Witken, 1985), which may further impair the immune system. This would have relevance in terms of promoting yeast growth and increasing the chances of additional infections from bacteria leading to antibiotic usage again.
Arabinose, Yeast and Autism
Shaw, Kassen & Chaves (1995), also identified high levels of arabinose in the urine of the autistic children. The exact biochemical role of arabinose is unknown, but a closely related yeast alcohol, arabitol has been used as a biochemical indicator of invasive candidiasis (Kiehn et al, 1979; Wong et al, 1990, Roboz & Katz, 1992). It is thought that arabitol produced by the yeast in the gut is absorbed into the portal circulation and then converted to arabinose by the liver. Elevated protein-bound arabinose has been found in the serum glycoproteins of schizophrenics (Varma & Hoshino, 1980) and in children with conduct disorders (Varma et al, 1983).
Arabinose reacts with the epsilon amino group of lysine in a wide variety of proteins and may then form cross-links with arginine residues in an adjoining protein (Sell & Monnier, 1989). Arabinose has therefore been implicated in protein modification via cross-linking the proteins and altering both biological structures and functions of a wide variety of proteins. Shaw et al (1999) has proposed that this may include proteins involved in the interconnection of neurons. Decreased clinical symptoms of autism after antifungal treatment might be due to decreased arabinose and pentosidine formation (cross-linked proteins described above). This would result in fewer random neural connections and increased numbers of neural connections that are oriented to the childs environment. The influence of a number of vitamins on candida activity and the operation of many metabolites of candida has been discussed (Mahler & Cordes, 1966). It is commonly found that children with autism experience improved symptoms following removal of gluten and casein from the diet (Shattock et al 1990, 1991, 1996, 1997; Reichelt et al, 1981, 1986; Knivsberg et al, 1990). It is unclear whether there is a link with arabinose and pentosidine formation, however given the wide distribution of these proteins in foods, there may be a relevant process involved with respect to autistic symptoms. Research into this may be useful.
Clostridia and Autism
Bolte (1998) outlined the possibility of a sub-acute, chronic tetanus infection of the gut as the underlying cause for symptoms of autism observed in some individuals. Here it is postulated that a percentage of individuals with autism have a history of extensive antibiotic use. As above it is known that oral antibiotics significantly disrupt protective gut microflora, creating a favourable environment for colonisation by opportunistic pathogens. Clostridium tetani is a ubiquitous anaerobic bacillus that is known to produce a potent neurotoxin. The normal site of binding for tetanus neurotoxin is the spinal cord, yet the vagus nerve is capable of transporting tetanus neurotoxin, providing a route of ascent from the intestinal tract to the central nervous system and bypassing the spinal cord. The result would be the typical symptoms of a tetanus infection would not be evident. Once in the brain the tetanus neurotoxin disrupts the release of neurotransmitters. This may explain the wide variety of behavioural deficits apparent in autism. Bolte (1998) presents evidence of lab animals exhibiting many of these behaviours after being injected in the brain with tetanus neurotoxin, and also of children with autism showing a significant reduction in stereotyped behaviour following treatment with antimicrobials effective against intestinal clostridia.
Shaw (1999) has developed a similar technique to yeast metabolite analysis by GC/MS for clostridia metabolites. While it has not been fully identified it has been shown that tyrosine derivative, a compound very similar but not identical to 3,4-dihydroyphenylpropionic acid is raised in the urine of children with various conduct disorders. It has also been pointed out that tyrosine, a substrate used by the body for the production of neurotransmitters, might imply that this unidentified product is important in altering key biochemical pathways for neurotransmitters in the brain. The relevance to autism remains unclear. Clearly a treatment to reduce the numbers of clostridia in the gut might help to reduce the effects of this inhabitation. However, clostridia are spore forming meaning re-colonisation is possible even after treatment. The relevance of probiotic and prebiotic treatments has not been researched, yet this appears a reasonable approach to aid suppression of the clostridia species.
Human Gut Flora and Gluten and Casein Intolerance in Autistic Children
Yeasts, including Candida albicans are known to secrete a number of enzymes. These may include phospholipase, which will break down phopholipids and proteases such as secretory aspartate protease which break down proteins. These enzymes may partially digest the gut membranes and lining itself. Furthermore, it is known that the mycelium and chlamydospore are capable of tissue invasion (Nolting et al, 1994). It is likely that such factors could increase the permeability of the gut. This has important consequences in terms of food absorption and digestion. In terms of autism symptoms this may be highly relevant. It has been shown that incompletely broken down portions of gluten and casein may be crossing the gut into the blood and having an opioid effect in autistic children. Their symptoms being a consequence of this opioid action (Reichelt, 1981; Shattock et al, 1990). While many mechanisms have been suggested for this incomplete breakdown, it seems key that a yeast and/or clostridia overgrowth would affect this in some way.
Products of the human gut microflora in relation to autism and its symptoms appear to have been largely ignored in the past. However they appear to be relevant certainly in terms of yeast and clostridia species. Abnormal bacterial metabolites of tyrosine appear to be elevated in autism and this seems related largely to an overgrowth in clostridia species. Treatments to control this have resulted in significant clinical improvement or complete remission of symptoms in some cases. The issue of whether probiotic and prebiotic treatments are relevant needs to be researched. Elevation of yeast metabolites such as tartaric acid and arabinose appears to be even more common in autism. The arabinose appears to be involved in abnormal protein binding which may adversely affect neuron connection and this may have relevance to the appearance of autistic symptoms. Given the intolerance autistic children appear to have to gluten and casein, an involvement of arabinose may be important. However, the exact biochemical role of arabinose remains unclear. Tartaric acid from the yeast overgrowth may have a direct toxic effect on the muscles and is a key inhibitor of the Krebs cycle that supplies raw materials for gluconeogenesis. The implications of this appear to be detrimental to autistic function.
While it is clear that abnormal metabolites from the human gut flora may contribute to autistic symptoms, it is certain that many other systems and pathways are involved. It is possible that many are functioning simultaneously but at varying levels between individuals. This may give rise to the differences in symptoms exhibited by sufferers. This may also explain the similarity of autism and other chronic behavioural disorders such as Asperger Syndrome, PDD, ADHD, ADD and Rett syndrome. While other pathways may exist, research into the role of human gut flora and the full identification of species involved may allow for more directed treatments. While it will not cure the disorder, modifications of gut flora function might improve symptoms significantly.
Bolte ER, (1998). Autism and Clostridium tetani. Medical Hypotheses 51(2): 133-144 [View abstract]
Danna P, Urban C, Bellin E and Rahal J, (1991). Role of Candida in pathogenesis of antibiotic associated diarrhoea in elderly patients. Lancet 337: 511-14.
Gupta S, Aggarwal S and Heads C (1996). Dysregulated immune system in children with autism: beneficial effects of intravenous immune globulin on autistic characteristics. Journal of Autism and Developmental Disorders 26(4): 439-52.
Holzapfel WH, Haberer P, Snel J, Scillinger U, Jos HJ, Velt Hi, (1998). Overview of gut flora and probiotics. International Journal of Food Microbiology 41: 85-101.
Kanner L, (1943). Autistic disturbances of affective contact. The Nervous Child 2: 217-250.
Kiehn T, Bernard E, Gold J & Armstrong D, (1979). Candidiasis: detection by gas-liquid chromatography of D-arabitol, a fungal metabolite, in human serum. Science 206: 577-580.
Kinsman OS and Pitblado K, (1989). Candida albicans gastrointestinal colonization and invasion in the mouse: effect of antibacterial dosing, antifungal therapy, and immunosuppression. Mycoses 32: 664-74.
Knivsberg A-M, Wiig K, Lind G, Nødland M & Reichelt K-L, (1990). Dietary Intervention in Autistic Syndromes. Brain Dysfunction 3: 315-327.
Kontstanareas M and Homatidis S, (1987). Ear infections in autistic and normal children. Journal of Autism and Developmental Disorders 17: 585
Kennedy M and Volz P (1983). Dissemination of yeasts after gastrointestinal inoculation in antibiotic-treated mice. Sabouradia 21: 27-33.
Mahler H & Cordes E (1966). Biological Chemistry. Harpur and Row, New York pp 322-375.
Nolting S, Guzek B, Hauss R, (1995). Mykosen des Verdauungstraktes, Med. Wiss. Mediendienst Hamburg.
Ostfeld E, Rubinstein E, Gazit E and Smetana Z, (1977). Effect of systemic antibiotics on the microbial flora of the external ear canal in hospitalized children. Pediatrics 60: 364-66.
Podzorski R, Herron M, Fast D & Nelson R (1989). Pathogenesis of candidiasis. Immunosuppression by cell wall mannan catabolites. Archives of Surgery 124: 1290-1294.
Reichelt K-L, Saelid G, Lindback T & Boler JB, (1986). Child Autism: a complex disorder. Biological Psychiatry 21: 1279-1290.
Reichelt K-L, Hole K, Hamberger A, Saelid G, Edminson PD, Braestrup CB, Lingjaerde P & Orbeck H, (1981). Biologically active peptide containing fractions in schizophrenia and childhood autism. Advances in Biochemical Psychopharmacology 28: 627-643.
Roboz J & Katz R, (1992). Diagnosis of disseminated candidiasis based on serum D/L arabinitol ratios using negative chemical ionisation mass spectrometry. Journal of Chromatography 575: 281-286.
Shah D & Larsen B, (1992). Identity of a Candida albicans toxin and its production in vaginal secretions. Medical Science Research 20: 353-355.
Shah D & Larsen B, (1991). Clinical isolates of a yeast produce a gliotoxin-like substance. Mycopathologica 116: 203-208.
Samonis G and Dassiou M, (1994a). Antibiotics affecting gastrointestinal colonization of mice by yeasts. Chemotherapy 6: 50-2.
Samonis G, Gikas A and Toloudis P, (1994b). Prospective evaluation of the impact of broad-spectrun antibiotics on the yeast flora of the human gut. European Journal of Clinical Microbiology & Infectious Diseases 13: 665-7.
Samonis G, Gikas A and Anaissie E, (1993). Prospective evaluation of the impact of broad-spectrun antibiotics on gastrointestinal yeast colonization of humans. Antimicrobial Agents and Chemotherapy 37: 51-53.
Sell D & Monnier V, (1989). Structure elucidation of a senescence cross-link from human extracellular matrix. Implications of pentoses in the aging process. Journal of Biological Chemistry 264: 21597-21602.
Shattock P & Savery D, (1997). Autism as a Metabolic Disorder. Autism Research Unit, University of Sunderland, Sunderland, UK. [Link]
Shattock P & Savery D, (1996). Urinary profiles of people with autism: Possible implications and relevance to other research. In: Proceedings of Conference on Therapeutic Interventions in Autism: Perspectives from Research and Practice. 309-325.
Shattock P & Lowdon G, (1991). Proteins, Peptides and Autism. Part 2: Implications for the education and care of people with autism. Brain Dysfunction 4(6): 323-334.
Shattock P, Kennedy A, Rowell F & Berney T, (1990). Role of neuropeptides in autism and their relationships with classical neurotransmitters. Brain Dysfunction 3: 328-345.
Shaw W, Baptist J, Geenens D, (1999). Immunodeficiency, gastrointestinal Candidiasis, wheat and dairy sensitivity, abnormal urinary arabinose and autism: a case study. Unpublished: Great Plains Laboratory, Overland Park, Kansas 66204.
Shaw W, (1999) Role for certain yeast and bacteria byproducts discovered by organic acid testing in the etiology of a wide variety of human diseases. Bulletin of The Great Plains Laboratory. Overland park, KS 66204 (913) 341-8949.
Shaw, W and Chaves E, (1996). Experience with organic acid testing to evaluate abnormal microbial metabolites in the urine of children with autism. Published in: The Proceedings of the Autism Society of America National Conference on Autism. Milwaukee: Wisconsin.
Shaw W, Kassen E and Chaves E, (1995). Increased excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clinical Chemistry 41: 1094-1104.
Van der Waaij D, (1987). Colonization resistance of the digestive tract–mechanism and clinical consequences. Nahrung 31: 507-17.
Varma R & Hoshino AY, (1980). Serum glycoproteins in schizophrenia. Carbohydrate Research. 82(2): 343-51.
Varma R, Michos GA, Gordon BJ, Varma RS, Shirey RE (1983). Serum glycoconjugates in children with schizophrenia and conduct and adjustment disorders. Biochemical Medicine. 30(2): 206-14.
Witken S (1985). Defective immune responses in patients with recurrent candidiasis. Infections in Medicine May/ June pp 129-132.
Wong B, Brauer K, Clemens J & Beggs S, (1990). Effects of gastrointestinal candidiasis, antibiotics, dietary arabinitol, and cortisone acetate on levels of Candida metabolite D-arabitol in rat serum and urine. Infection and Immunity 58: 283-288.
* The Childhood Autism Rating Scale, an observational measure of various aspects of autism, for the child in question decreased from 43 (severely autistic) prior to introduction of these therapies to a value of 29 (non-autistic) after therapy.