Autism and allergies

8 Oct

ResearchBlogging.orgAllergies are often a topic of discussion in the autism community. Much of the alternative- medicine approach works from the point of acting on allergies. I saw this paper and found it interesting, but wasn’t going to blog it until the PETA campaign (Got Autism) came up using the proposed sensitivity of autistics to casein.

The paper is Atopic features in early childhood autism, by B. Bakkaloglu, B. Anlar, F.Y. Anlar, F. Oktem, B. Pehlivantürk, F. Una, C. Ozbesler, and B. Gökler. As you might guess from the author list, this isn’t a U.S. or western European group. They are from Turkey. I have no reason to doubt the group’s quality, but that fact, together with the fact that the sample size is relatively small (30 autistic and 30 controls), suggests to me that this isn’t going to be the final word on this subject.

That said, the paper looks for allergic hypersensitivity (atopy) in a group of children with autism.

Here’s the abstract:

BACKGROUND: Autism is a developmental disorder of unknown etiology. Sensitivity to dietary and environmental antigens has been considered in its pathogenesis.

AIM: To examine immediate hypersensitivity in early childhood autism.

METHODS: We investigated 30 autistic children (23 boys, seven girls 2-4 years old) for atopic history, serum IgG, IgA, IgM, IgE levels, and skin prick tests (SPT) with 12 common antigens.

RESULTS: Nine/30 autistic children (30%) and 1/39 (2.5%) age-matched neurological controls from the same hospital had a family history suggestive of atopy (p<0.005). No patient in the autism and 28% in control group had symptoms of respiratory allergy (wheezing or asthma) (p<0.005), and 6/30 (20%) autistic vs. 7/39 (17%) control children had history suggesting other allergic disorders (p=ns). Eleven/23 (47.8%) autistic children had at least one positive skin test, similar to age-matched population controls. Serum IgG, IgA, and IgM levels were within age-appropriate limits. Serum IgE was elevated in four patients (13.3%). Specific IgE levels were negative in four cases with multiple SPT positivity.

CONCLUSIONS: This study suggests allergic features based on history, skin tests, and serum IgE levels are not frequent in young autistic children despite family history. This discrepancy between predisposition and manifestation might imply immunological factors or environmental condition

That gives away the punch-line: they don’t see a correlation between allergic features and autism. It’s still worth looking a bit closer at the paper.

They recognize that autism is a broad spectrum, so they attempted to look at a group that was fairly similar:

Many studies examined hypersensitivity or intolerance to environmental and food antigens in autism: however, their interpretation and comparison may be difficult due to methodological differences or anecdotal nature of the information. In addition, autistic spectrum disorders are a mixed group: inclusion of patients of various ages and clinical phenotypes can cause discrepancies, which we intended to avoid by studying newly diagnosed cases with idiopathic childhood autism in a narrow age range.

The study looked at very young children, ages 2-4. Autism was measured by a CARS test. Autistic children had scores from 33-50, with a median of 44.5. Since a score of 30-36.5 is considered “mild/moderate” autism, these data indicates that the children were largely in the “severe” range.

They found that 30% of the autistic children had familial history of atopy, compared with only 2.5% of the control children. However, autoimmune disease was not present in high numbers in the parents. Those two facts are interesting on their own, and if that was the end of the study, I wouldn’t be surprised if it popped up in autism discussion forums. But, another interesting finding is that the atopy is not found in the autistic children.

The questionnaire for allergic symptoms indicated familial atopy in 30% of autistic children and 2.5% of hospital controls (p<0.005) (Table 1). Taken together, 3/30 children of the autism group (10%) and 15/39 of the hospital controls (61%) had a score of at least 1 (p<0.005), and the rate of reported allergic symptoms was 6/30 vs. 7/39 (p:ns). Groups did not differ significantly in early-life environmental factors likely to affect allergic state: area of residence, day care attendance, breast feeding, and birth order. Parental autoimmune disease was present in two autism (vitiligo, psoriasis) and one control case (arthritis) (p:ns). CARS scores of the autism group were 33–50, mean 43.6, and median 44.5.

But, given that my interest level was higher due to the PETA ads using the proposed casein sensitivity of autistics, I wanted to see what sensitivities they found:

Of total 276 skin tests applied, 27 (9.7%) were positive, most commonly against aspergillus and grass antigens, followed by cat fur and D. farinae. Eleven/23 (47.8%) of children who received skin tests had a positive result with at least one antigen and five of them, with multiple antigens. House dust mite sensitivity was seen in three (13%), pollen, five (21.7%), and mold, in six (26%) children.

Serum IgG, IgA, and IgM were within age-appropriate limits according to laboratory standards. Serum IgE was elevated in 4/30 cases (13.3%), all associated with allergic symptoms in the patient or in a family member, or SPT positivity. Antigen-specific IgE tests done in four out of five children with multiple SPT positivity were negative.

So, mold (aspergillus), grass, cat fur and dust mites (D. farinae) were the top. Not casein, not gluten.

Again, do I think this is the last word on autism and allergies? No. But, I do think it is a good example of newer studies than, say, PETA’s reliance on a 1995 paper.

PETA appears to have wanted just enough data to justify their billboard. I join many in the blogging community who found the use of people with autism–the misuse, I should say–abhorrent. Kev has already responded in his own way. It took me a while to find my own, rather obscure, method of response.

I am grateful that the billboard has been pulled. I would hope that PETA would issue an apology as well. I’m not holding my breath.

B BAKKALOGLU, B ANLAR, F ANLAR, F OKTEM, B PEHLIVANTURK, F UNAL, C OZBESLER, B GOKLER (2008). Atopic features in early childhood autism European Journal of Paediatric Neurology, 12 (6), 476-479 DOI: 10.1016/j.ejpn.2007.12.008

67 Responses to “Autism and allergies”

  1. alyric October 14, 2008 at 00:50 #

    pd :

    You wrote:

    “I was much more interested in showing that Alyric was basing his rather authoritative statements on assumptions and the lack of investigation, as opposed to actual research.”

    Oh no you dont;. No assumptions there and we’re missing exactly one reference and i’m working on that one. Meanwhile you and Maria can stop walking round the elephant in the room and explain how the leaky gut phenomenon as applied to autism and involving macromolecules works without the kids ending up dead – as Gershon explains. Given his credentials, he ought to know.
    maria – do any of your cited references demonstrate either the loss or gain across the gut of macromolecules? Otherwise, they aren’t all that useful.

  2. M Luján October 14, 2008 at 14:02 #

    alyric, other comment caught by spam …
    Do you know about transcytosis?
    Transcytosis: Crossing the Cellular barriers

  3. M Luján October 14, 2008 at 14:57 #

    Ay Alyric
    Why don´t you read at least the abstracts of what I posted, please?or the titles of the references?

    In the intestine of suckling rodents and in the human placenta, the MHC class I–related Fc-receptor for IgG, FcRn, mediates transport of IgG across epithelial barriers by transcytosis. Transepithelial transport by FcRn explains how humoral immunity transfers from mother to infant. After weaning, however, epithelial cells of the rodent intestine downregulate expression of FcRn to nearly undetectable levels, and adult rodents do not absorb orally administered IgG. In contrast, absorptive epithelial cells lining the intestine of humans continue to express FcRn in adult life (14), and when tested in vitro, human, canine, and rodent epithelial cells in culture that express FcRn exhibit FcRn-dependent transcytosis of IgG in both directions across the epithelial monolayer (15–17). Based on these data, we recently proposed that FcRn may function in the adult human to shuttle IgG or IgG-antigen complexes across epithelial barriers for immune surveillance, host defense, or both

    From
    Receptor-mediated Immunoglobulin G Transport Across Mucosal Barriers in Adult Life : Functional Expression of FcRn in the Mammalian Lung The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002 303-310
    and how do you think botulin toxin reached blood

    J Pharmacol Exp Ther. 2005 Dec;315(3):1028-35.Visualization of binding and transcytosis of botulinum toxin by human intestinal epithelial cells.Ahsan CR, Hajnóczky G, Maksymowych AB, Simpson LL.
    Botulinum toxin is an unusually potent oral poison, which means that the toxin must have an efficient mechanism for escaping the lumen of the gut to reach the general circulation. Previous work involving iodination of toxin and analysis of its movement demonstrated a specific process of transepithelial transport. In the present study, botulinum toxin labeled with Alexa Fluor 488 was used to visualize the discrete steps of binding, internalization, transcytosis, and release. The data revealed that binding sites for the toxin were distributed across the apical surface of epithelial cells, and there was no evidence of significant clustering. The amount of toxin bound to receptors at saturation was too large to be accommodated in a single wave of endocytosis. Toxin that entered epithelial cells did not remain in the vicinity of the endocytosing membrane, which is in striking contrast to events in neuronal cells. Instead, the toxin began to spread across the length of cells, eventually being released on the basolateral surface. Migration of toxin through epithelial cells required redistribution to the cell periphery. This migration pattern could be attributed to the large and centrally located nucleus, which physically displaced transport vesicles. Transcytosed toxin began to reach the contralateral surface within ca. 5 min, and transcytosis was essentially complete within 20 to 30 min.

    These studies demonstrate unique host cell adherence contacts, early endocytosis-specific structures, and a presumptive exocytosis component of this transcellular transcytosis route.

    Infect Immun. 2008 Sep 2.
    Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence to, Invasion into, Translocation across, and Exocytosis from Polarized Human Intestinal Caco-2 Cells.Hu L, Tall BD, Curtis SK, Kopecko DJ.

    This effect was associated with changes in expression of the tight junction proteins occludin and claudin-1. These data suggest that IFNgamma selectively increases the transepithelial flux of large molecules by activating specific pathways within the junctional pore. One hypothesis is that this process may be activated in the early stages of the inflammatory response, facilitating the passage of large and potentially antigenic molecules across the gut without gross disruption of the barrier to small molecules.

    J Cell Sci. 2005 Nov 15;118(Pt 22):5221-30. Epub 2005 Oct 25.
    Interferon-gamma selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores.Watson CJ, Hoare CJ, Garrod DR, Carlson GL, Warhurst G.

    The levels of IL-12 and IFN-gamma were significantly (P < or = 0.05) higher in patients as compared to controls.

    from Singh et al, 1996.
    Remember the literature on immune dysfunction (P. Ashwood), different microflora in ASD vs controls (Several manuscripts) and works of Dr Buie et al on digestive enzymes-to begin with.
    THE TOPIC DESERVES FURTHER RESEARCH properly done with more sophisticated questions with updated knowledge

  4. M Luján October 14, 2008 at 15:26 #

    Med Mol Morphol. 2007 Mar;40(1):1-7. Molecular morphology of the digestive tract; macromolecules and food allergens are transferred intact across the intestinal absorptive cells during the neonatal-suckling period.Fujita M, Baba R, Shimamoto M, Sakuma Y, Fujimoto S.
    Food allergies represent an important medical problem throughout the developed world. The epithelium of the digestive tract is an important area of contact between the organism and its external environment. Accordingly, we must reconsider the transport of intestinal transepithelial macromolecules, including food allergens, in vivo. The intestinal epithelium of the neonatal-suckling rat is a useful model system for studies into endocytosis and transcytosis.Macromolecules and food allergens can be transferred intact with maternal immunoglobulins across the absorptive cells of duodenum and jejunum during the neonatal-suckling period. This review summarizes these observations as well as our recent molecular morphological studies.

  5. alyric October 15, 2008 at 14:10 #

    Maria

    Thanks for the references, but it would also be good if you read them too:) That way, you would realise that transcytosis as per the reference you cite is a highly controlled process, which in the gut refers to the transport of immunoglobulins and vitamins like B12.

    I wrote to Professor Mike Gershon and here’s what the good Professor had to say:

    “I reasoned that if there was a leak of protein into the lumen of the bowel, a protein losing enteropathy would result because the lumen of the gut is essentially out of the body. If protein enters the gut lumen, blood albumin falls, and the body swells. There is no hint of such a syndrome in autism. It has never been reported. I am, however, engaged right now in a direct investigation of the issue.”

    So, I did misread or more likely misinterpret what I read – my bad. However your bad and pd’s as well is to come up with all these sophisticated papers having to do with increased permeability and a whole lot just describing the mechanisms of transport of larger molecules. The elephant is still standing – how do you explain, and none of these references do how uncontrolled (tyranscytosis is a very controlled process) movement of large molecules does not result in death and pretty damn quickly at that. Gershon isn’t kidding about the albumin problem. To give you some idea – i have some small protein loss through the kidneys – causing oedema. Imagine such a phenomenon spread over the gut. Sorry folks – imcompatible with life.

    Interesting to see what Gershon comes up with.

  6. passionlessDrone October 15, 2008 at 15:04 #

    Hi Alyric –

    I reasoned that if there was a leak of protein into the lumen of the bowel, a protein losing enteropathy would result because the lumen of the gut is essentially out of the body. If protein enters the gut lumen, blood albumin falls, and the body swells. There is no hint of such a syndrome in autism. It has never been reported. I am, however, engaged right now in a direct investigation of the issue

    Well now this is getting richer by the minute. Your assumptions and his reasoning served up as quality science. Nice.

    1) Have you considered telling Gershon of your conclusion that the leaky gut theory is a sunk theory, as you proposed earlier? I’m sure he would be interested in your opinion. You also ought to explain to him that by your reasoning, he needs to be looking for dead people to study if he wants to find any positive results. [How can he not see that elephant in the room?]

    2) What an absolutely perfect illustration of the doublespeak shrouding the issue of vaccines in this country. Lets contrast what he said, with what he presented to congress over seven years ago:

    “No movement of peptides or proteins from the tissue fluid to the intestine has been detected in autism or as a result of MMR vaccination”

    Technically true, as no studies have been done in one way or the other. Is he a researcher, or a used car salesman?

    My assertion is that there is insufficient evidence for a relationship between autism and increased permeability to be ruled out. This relationship need not be causal. Based on the fact that the highly esteemed Gershon is at this moment conducting research on this, he would seem to agree with me, as opposed to you. LOL!

    . The elephant is still standing – how do you explain, and none of these references do how uncontrolled (tyranscytosis is a very controlled process) movement of large molecules does not result in death and pretty damn quickly at that. Gershon isn’t kidding about the albumin problem

    More bogus assumptions.

    The fact that there are neurological complications observed in some instances of celiac disease is well established and not controversial. The mechanism of action is not well understood. Celiacs are not dead, have documented increased permiability, and subsets have been shown to exhibit neurological disorder. The elephant is in your mind only.

    What evidence, other than your increasingly shaky assumptions, do we have to believe there is not a similar relationship in some autistic populations?

    Your second assumption is that the offending food actually entering the bloodstream could be the only thing that causes a problem in a situation of increased permeability. What if, instead, bacterial endotoxins can fit within the spaces created by increased permeability?

    Funny enough, you might be interested in knowing that children with identified food sensitivities exhibit greater intestinal permeability when they are challenged with those foods. See: “Gastrointestinal permeability in children with cow’s milk allergy: effect of milk challenge and sodium cromoglycate as assessed with polyethyleneglycols (PEG 400 and PEG 1000)” for more. There are others.

    Thus far, I have provided references for chronic stress, and foods known to generate immune responses increasing gut permeability. Likewise, we have evidence that children with autism are more likely to generate immune responses to common foods when compared to non diagnosed peers. We also have evidence of increased stress response in autism. You have provided reasoning, a study that is currently ongoing, and assumptions.

    Keep it up. You are making my point for me.

    – pD

  7. alyric October 15, 2008 at 23:00 #

    I doubt that I’m making any point for you, considering how you sidestep that elephant. I don’t know your background and frankly I doubt that it’s in the life sciences. Not, mind you that I’m all that far ahead. I consider I’ve forgotten practically all the biochemistry I ever knew.

    You wrote:

    “No movement of peptides or proteins from the tissue fluid to the intestine has been detected in autism or as a result of MMR vaccination”

    Technically true, as no studies have been done in one way or the other. Is he a researcher, or a used car salesman?

    Pardon me but your ignorance of some very basic human physiology is showing. I hope you don`t mind if I find it exasperating.
    You have a layman’s view of assumptions, not seeming to understand what obstacles the leaky gut theory of autism causation must overcome. Somehow, you confuse opinion with fact. There are several physiological facts that Gershon pointed out. These are not assumptions, no matter how you slice and dice it. Loss of protein has consequences. If this is to any even small degree, given the overall size of the intestines, then the person is dead. No way, that this scenario is compatible with life. I’m glad that Gershon is tackling this issue, because no one else has, that’s for sure. But and here’s the crunch, this theory is sunk not merely because one as yet unassailable physiological characteristic of humans has yet to be confirmed in this situation, it’s sunk for all the reasons (physiological ones) that Gershon raises. This theory is not compatible with human life. Lord, read Maria’s reference on transcytosis. Brother, did that bring back memories, but it’s a good overall look at the kinds of things that get across membranes and how they did it. If the leaky gut theory had legs, it should be possible to bring those sorts of molecules through the first barrier through some as yet unknown mechanism. It remains undiscovered and as Gershon has reasoned, highly unlikely to be discovered. This has been a lovely discussion and we should continue it, especially if you can find a reference that might resurrect the theory.

    By the way, allergies and permeability is a whole nuther subject. Look at transcytosis of Ig’s involving Peyer’s Patches – very interesting. I hope your’e not getting yourself confused by mixing up immunoglobulins with just any old macromolecule. The body doesn`t work in such a fashion, and a good thing too. Also in case of Igs being transported, there is no need for a leaky gut at all. That seems to be why we have Peyer`s Patches and a reasonable explanation for the idea that kids who eat – well a range of bodily excretions have the most robust immune systems:)

    I suppose I should answer this as well

    You wrote (and I wish you hadn`t)

    `The fact that there are neurological complications observed in some instances of celiac disease is well established and not controversial. The mechanism of action is not well understood. Celiacs are not dead, have documented increased permiability, and subsets have been shown to exhibit neurological disorder.“

    Well, they don`t have a leaky gut do they, so why would there be a problem. If you`re going to raise `permeability`then the question is to what. And holy cow, you don`t want to think of being open to bacterial toxins. Do you have any idea of the levels of bacterial toxins in the gut. Also, the work they`ve done on Parkinsons and Alzheimers and gut problems is putting some interesting hypotheses about but note that these are associative and not causative.

  8. alyric October 16, 2008 at 00:48 #

    pd, you got me curious so I looked it up. E Coli is about the commonest of enteric bacteria and one of the many subtypes produces a toxin. The molecular weight is 66kDa. The molecular weight of albumin is from 66 – 69 kDa. In other words, the sizes are about the same, which leads us right back to Gershon and why this is a sunk theory twice over if you happen to be postulating permeability large enough to admit such molecules. Just for comparison the Chlostridium botulinum toxin has a molecular weight of 150kDa, or about two and a half times the size of albumin.

    There are holes in this theory you could drive a truck through (analogy intended).

  9. passionlessDrone October 16, 2008 at 01:12 #

    Hi Alyric –

    I doubt that I’m making any point for you, considering how you sidestep that elephant.

    LOL! If having a leaky gut is incompatible with human life, WHY IS GERSHON INITIATING A STUDY OF IT RIGHT NOW? WHY? WOULDN’T ALL OF THE SUBJECTS POSSIBLE FOR A POSITIVE FINDING ALREADY BE DEAD?

    I consider I’ve forgotten practically all the biochemistry I ever knew.

    I believe you.

    No movement of peptides or proteins from the tissue fluid to the intestine has been detected in autism or as a result of MMR vaccination

    I didn’t say this, Gershon said it, to Congress. Follow the link that Regan posted for more. It is, in all likelyhood, this quote that made you come up with your belief than an ‘intensive’ study had been done looking for blood proteins in the intestine.

    I hope you don`t mind if I find it exasperating.

    LOL!

    You have a layman’s view of assumptions, not seeming to understand what obstacles the leaky gut theory of autism causation must overcome.

    You have quoted specific pieces of my response, but it isn’t clear what, if any of them, you have actually read. I was quite clear when I said “This relationship need not be causal.” Perhaps in your background in the life sciences, they didn’t teach you what a sentence like this means?

    But and here’s the crunch, this theory is sunk not merely because one as yet unassailable physiological characteristic of humans has yet to be confirmed in this situation, it’s sunk for all the reasons (physiological ones) that Gershon raises

    Then why is he studying it further? Why? To convince me?

    You said: Interesting to see what Gershon comes up with.

    Why do you believe the results will be interesting? What do you possibly hope to understand by analyzing his results?

    Well, they don`t have a leaky gut do they, so why would there be a problem. If you`re going to raise `permeability`then the question is to what.

    What is leaky gut, if not increased permiability? I also cannot help but notice that you fail to dispute the well established neurological outcomes in some patients with celiac disease.

    Also, the work they`ve done on Parkinsons and Alzheimers and gut problems is putting some interesting hypotheses about but note that these are associative and not causative.

    We are in agreement!

    – pD

  10. M. Luján October 17, 2008 at 22:56 #

    Well, three comments, trapped…
    I will try with this, a repeated one.
    Do you know about translocation?
    Not only the diagnosis of leaky gut is present but also is sometimes treated….

    Neuro Endocrinol Lett. 2008 Feb;29(1):117-24. Links
    The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.
    Maes M, Kubera M, Leunis JC.
    There is now evidence that major depression (MDD) is accompanied by an activation of the inflammatory response system (IRS) and that pro-inflammatory cytokines and lipopolysacharide (LPS) may induce depressive symptoms. The aim of the present study was to examine whether an increased gastrointestinal permeability with an increased translocation of LPS from gram negative bacteria may play a role in the pathophysiology of MDD. Toward this end, the present study examines the serum concentrations of IgM and IgA against LPS of the gram-negative enterobacteria, Hafnia Alvei, Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae in MDD patients and normal controls. We found that the prevalences and median values for serum IgM and IgA against LPS of enterobacteria are significantly greater in patients with MDD than in normal volunteers. These differences are significant to the extent that a significant diagnostic performance is obtained, i.e. the area under the ROC curve is 90.1%. The symptom profiles of increased IgM and IgA levels are fatigue, autonomic and gastro-intestinal symptoms and a subjective feeling of infection. The results show that intestinal mucosal dysfunction characterized by an increased translocation of gram-negative bacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. It is suggested that the increased LPS translocation may mount an immune response and thus IRS activation in some patients with MDD and may induce specific “sickness behaviour” symptoms. It is suggested that patients with MDD should be checked for leaky gut by means of the IgM and IgA panel used in the present study and accordingly should be treated for leaky gut.
    Neuro Endocrinol Lett. 2007 Dec;28(6):739-44. Normalization of the increased translocation of endotoxin from gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome.
    Maes M, Coucke F, Leunis JC.
    There is now evidence that chronic fatigue syndrome (CFS) is accompanied by an increased translocation of endotoxins from gram-negative enterobacteria through the gut wall, as demonstrated by increased prevalences and median values for serum IgM and IgA against the endotoxins of gram-negative enterobacteria. This condition can also be described as increased gut permeability or leaky gut and indicates intestinal mucosal dysfunction (IMD). Here we report a case of a 13 year old girl with CFS who showed very high values for serum IgM against the LPS of some enterobacteria and signs of oxidative and nitrosative stress, activation of the inflammatory response system, and IgG3 subclass deficiency. Upon treatment with specific antioxidants and a “leaky gut diet”, which both aim to treat increased gut permeability, and immunoglobins intravenously, the increased translocation of the LPS of gram negative enterobacteria normalized and this normalization was accompanied by a complete remission of the CFS symptoms.

    Now, alyric, things are very much complicated that how you oversimplified them….

  11. M. Luján October 18, 2008 at 14:35 #

    Gut barrier function is maintained by a well-balanced intestinal flora, an intact mucosa, and a normal functioning immune system. If one or more of these three protective mechanisms are disrupted, viable bacteria [or bacterial products like endotoxin (i.e. lipopolysaccharide, LPS)] may cross the gut mucosa and spread to the mesenteric lymph nodes or more distant organs, such as the liver and the spleen, a process termed bacterial translocation.28 Three mechanisms have been suggested to explain the phenomenon of bacterial translocation: altered intestinal barrier function, bacterial overgrowth, and impaired host defence. Although bacterial translocation is widely considered a pathological and potentially harmful phenomenon, translocation of gut bacteria appears to be common early in life and may be important for mucosal antigen sampling in the gut.29

    It is known from a long time ago…
    Gastroenterology. 1994 Sep;107(3):643-
    The prevalence of gut translocation in humans.
    Sedman PC, Macfie J, Sagar P, Mitchell CJ, May J, Mancey-Jones B, Johnstone D.
    Combined Gastroenterology Unit, Scarborough District Hospital, North Yorkshire, England.
    BACKGROUND/AIMS: Gut translocation of enteric organisms across the intact intestinal mucosa has been postulated as a potential source of sepsis in susceptible patients. However, little is known of its occurrence or significance in humans. The aim of this study was to determine the prevalence of gut translocation of bacteria in humans and attempt to identify any predisposing factors to its occurrence. METHODS: A consecutive series of 267 general surgical patients were examined for evidence of bacterial translocation by bacterial analysis of intestinal serosa and mesenteric lymph nodes taken at the time of surgery. RESULTS: Translocation occurred in 10.3% of patients overall. Both aerobic and anaerobic bacteria translocated. Excluding patients with distal intestinal obstruction and those with inflammatory bowel disease in whom translocation was more common, the prevalence was 5%. Neither jaundice, nutritional status, nor total parenteral nutrition predisposed to translocation. Similarly, mucosal atrophy did not predispose to this phenomenon. The development of postoperative septic complications was twice as common in patients with translocation as in those without, but mortality was unaffected. CONCLUSIONS: Translocation occurs as a spontaneous event in humans, but its clinical significance remains to be defined.

    Disruption of an intact intestinal epithelial barrier has been recognized to play important pathophysiologic roles in both CD (42, 77) and UC (73). For example, the expression of occludin, an epithelial intercellular tight-junction compound protein, was markedly down-regulated in active IBD, and this was paralleled by a locally pronounced leukocyte transmigration rate (46). As a consequence of impaired barrier integrity, enteric bacteria are enabled to traverse the epithelial lining, thus enhancing antigenic exposure to immune and nonimmune cells located in deeper mucosal compartments. This process results in aggravation and chronification of mucosal inflammation, which in turn further compromises the barrier function of the intestinal epithelium (49). In the setting of a disrupted epithelial barrier, microbial encounters normally residing in the bowel lumen are enabled to translocate to the mucosal and submucosal layers (72). Having reached this subepithelial compartment, microbia will normally be recognized by pathogen-associated molecular pattern (PAMP) receptors, including Toll-like receptors, which are expressed by mucosal immune and nonimmune cells. These cell populations include macrophages, neutrophils, and dendritic cells, as well as intestinal myofibroblasts (63) and EC (52) (Fig. 1). In addition to their function as a second mechanical line of defense, EC are able to rapidly mount an innate immune response (10, 57), serving a sentinel function by communicating with other local immune cell populations

    MINIREVIEW
    Intestinal Microvascular Endothelium and Innate Immunity in Inflammatory Bowel Disease: a Second Line of Defense?
    Infection and Immunity, October 2006, p. 5425-5432, Vol. 74, No. 10
    Please see figure 1…
    AGaim alyric, I never told you about the lack of control in the transcytosis, but my concern was to present that the control system may be affected….and what other processes are involved

    The impact of bacterial adhesion on translocation across the epithelium represents another recurrent question. Translocation of commensal bacteria to mesenteric lymph nodes (MLN)6 has been clearly demonstrated (29–32) and presumably is central to the development and activation of the intestinal immune system. This work should be expanded to screen a wide range of well-characterized and labeled probiotic strains, considering that some strains may be capable of modulating tight junctions and thereby crossing the epithelium

    The American Society for Nutrition J. Nutr. 137:781S-790S, March 2007
    Cross-Talk between Probiotic Bacteria and the Host Immune System1,2
    Blaise Corthésy3, H. Rex Gaskins4 and Annick Mercenier5

  12. dr treg October 20, 2008 at 16:52 #

    A.D. is considered to be the result of an abnormal immunogenic response in genetically predisposed children. Structural and functional changes have been noted in

    1. Neuronal dendrites

    2. The gastro-intestinal tract

    CD3, interleukins, IgA and enzyme abnormalities in the gastro-intestinal system have been described.

    http://autism.suite101.com/article.cfm/gastrointestinal_problems_in_asd

    Statistically, immunogen exposure after delivery as a cause of A.D. is most likely to originate in the g-i tract. The immunogen could be dietary comonents, whole/partial organisms e.g. bacteria or toxins e.g. L.P.S. etc

    The question is

    Are the inflammatory changes in the g-i tract primary in A.D.i.e. is the g-i tract inflammed because of the underlying disease?
    i.e. the g-i tract is a lynchpin in the origin of the immunogenic response
    or
    Does a g-i tract immunogenic response develop after the original immunogenic response?
    i.e. the g-i tract is an innocent bystander

    Celiac disease is associated with white matter M.R.I. scan abnormalities and neuropathy so it is not inconceivable that is some children with A.D. the immunogenic response in the g-i tract is central to the development of A.D. However other children with A.D. will have other causes of the immunogenic response e.g. hyperphenylalaninemia in P.K.U., rubella, fetal-alcohol syndrome where the g-i tract changes are not thought to be primary in the development of A.D.
    A.D. seems increasingly to be an umbrella term for several different immuno-genetic diseases and current technology has only just started to unravel the immunology, genetics and neuroscience of A.D.

    Why not try sensible non-harmful dietary manipulation for food allergy, food sensitivity or food intolerance while double-blind controlled clinical trials and further scientific research are awaited?

  13. passionlessDrone October 21, 2008 at 02:05 #

    Hi Dr. Treg –

    Why not try sensible non-harmful dietary manipulation for food allergy, food sensitivity or food intolerance while double-blind controlled clinical trials and further scientific research are awaited?

    Very concisely stated. Well done.

    – pD

  14. Joseph November 10, 2009 at 01:01 #

    @vitiligo is stealth spam.

    • Sullivan November 10, 2009 at 01:24 #

      thanks, Joseph. The comment has been deleted.

  15. カルティエ タンク September 17, 2013 at 03:01 #

    パシャ カルティエ カルティエ タンク http://www.868a1.com/

Trackbacks/Pingbacks

  1. Early Baby Foods Prepare Your Child for Life « Wicked Blogging - July 31, 2009

    […] Autism Blog – Autism and allergies « Left Brain/Right Brain […]

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this: