SearchingEquilibrium

I am the mom of an autistic child. In the needed learning to be the best mom he deserves I have found also the need to research, to exchange opinions and to learn in this journey doing a path and always searching equilibrium.

Sunday, March 11, 2007

Some comments in Gastrointestinal issues in ASD

You know, I have prepared a long – and I say LONG- post about published science in gastrointestinal issues in autism as concomitant medical problem (CMP), including all the topics on my previous post. But somehow, I was not convinced about. I feel I was lacking the key questions to answer, trying to present a very much wide picture- and therefore what I wanted to say would be diluted with much information not so important.
Therefore I focused on the questions I presented in my previous post.

The no written sentence in all cases is: “We need more high quality, high level research done by high level and commited scientists to confirm anecdotical evidence and previous clues in autism“. If you are interested, I can send the expanded version- much longer with all the proper citations in which I based these analysis (Or please let a comment therefore I include the link). Thanks

No cause/cures implications. For now, they are CMP that SHOULD be screened, tested, diagnosed and treated SUCH as in the case of non-autistics, IMHO. For me, another aspect of the advocate for my son I am, and yes he had several of the gut conditions I mention-now properly screened, tested, diagnosed and treated.
In bold, remarks and (partial) conclussions- or better opinions about potential conclussions-, in normal the manuscript´s findings and in italics my comments.

1-In general, autistic children/teens/adults have gastrointestinal issues more than non-autistic children/teen/adults?
One of the most recent published manuscripts form the Dr Horvath group (2002) reported for 36 children with ASD symptoms like chronic diarrhea, abdominal discomfort and distension. The histological examination revealed grade I or II reflux esophagitis in 69.4 % (25/36), chronic gastritis in near 40 %(15/36) and chronic duodenitis in near 66.6 % (24/36). Twenty two of the 25 children with reflux (88%) had night awakenings, signs of abdominal disconfort and pushing on the abdomen. None of the patients had H. Pylori.
Low intestinal carbohydrate digestive enzyme activity was reported in 21 children of 36 (58.3 %), even when no abnormality was found in pancreatic function. 27 of 36 children had an increased pancreatico billiar fluid output after intravenous secretin administration. 21 of 36 children had diarrhea (near 60 %). Low lactase was found in 14 patients. One kind of cells, the Paneth cells, showed similar results to studies done to Chron´s patients.
Kushak R and Buie T reported lactase deficiency in 58-65 %, isomaltase/palatinase deficiency in 30 to 40 % in ASD. Children with intestinal inflamation are 77 % deficient in lactase and 64 % in isomaltase.
Same author studied the possibility of GER (Gastroesophageal reflux) with GI complaints and aggression or self-injurious behavior GER was identified in 5 of 5 patients tested by wireless pH testing. Esophagitis was seen in 3 of 6 patients biopsied.
* pH testing data are reported in a scale called de Meester score. Normal is less than 14.72. Autistic Children showed from 19.7 to 75.1.
* Author concludes that aggressive or self injury behavior may be a manifestation of pain from GERD
And in adults the problem is generally underdiagnosed
Link

Data show quite distinct patterns of O-glycosylation within the glycocalix in children with autism, not simply due to inflammation.This may contribute to alterations in the colonic mucosal flora. As clinical improvement has been reported in autistic children when enteric dysbiosis is treated, these changes warrant further study if confirmed in larger series.
*The glycocalix is the polysaccharide-containing material (that is a covering of polymers of monosugars) lying outside the cells of the gut.
*Glycosylation is a process by which the glycocalix is modified by other sugars ( involving other enzymes for example). Abnormalities associated with disease states are major contributors to diversity in glycan expression
* It seems that not only inflammation, but altered glycosilation pathways of glycocalix can be found in gut in ASD.

…findings demonstrate a focal CD8-dominated gastritis in autistic children, with novel features. The lesion is distinct from the recently recognized focal gastritis of Crohn's disease, which is not CD8-dominated. As in the small intestine, there is epithelial deposition of IgG.

*CD8 is a glycoprotein- that is a protein with a sugar attached- When the cytotoxic T-Cells have a CD8 attached they are called CD8+Tcells. A cytotoxic T cell is a cell that can kill cells infected by viruses or other pathogens after activation.
*The epitelial deposition of IgG is suggestive of gut autoimmunity following Torrente et al.
*There are 7 medical conditions that can be related to milk/gluten/food allergies, not only Celiac disease, mediated by IgE or not. Food allergy is not the same as food intolerance.
*Suspected hypoacidity and gastroesophageal reflux can be present, specially if asthma is present
*There are acid and non-acid reflux and can be gastroesophageal or duodenogastric .

The development of non-IgE-mediated food allergies is associated with relatively subtle immunological abnormalities, including maturational delay in IgA, IgG subclass, CD8, and NK cell responses (Simon Murch Comment)- this is the topic of another post.

*Pancreatic deficiency affects more lipid digestion than protein digestion.
*There are published clues of carbohydrate, lipids and protein degradation problems in ASD (lack of enzymes, several organs of the digestive system malfunction).
*There are published clues of inflammation/immune activation in gut in ASD (Paul Ashwood recent work). These inflammation conditions includes: ileal lymphoid nodular hyperplasia-LNH- (and related), ileitis, colitis and colonic LNH, upper and lower gastrointestinal tract inflammation
*In almost all patients with heartburn, there is identifiable esophageal mucosal pathology, though only about 40% have endoscopically detectable erosions. The remaining 60% of patients with heartburn but no erosions have nonerosive GERD.
*Gastritis can be of different kinds. Although gastropathies may be mediated by inflammatory mechanisms, mucosal infiltration by polymorphonuclear or mononuclear cells is not necessary. The modern classification of gastritis incorporates etiology and morphologic and topographic mucosal changes
*Duodenitis is basically inflammation and irritation of the wall of the first part of the small intestine.
It is true that it has been published that the percentage of autistic children with GI issues was EXACTLY (9%) the same than non-autistic children with GI issues (BMJ. 2002 Aug 24;325(7361):419-21.
Relation of childhood gastrointestinal disorders to autism: nested case-control study using data from the UK General Practice Research Database.Black C, Kaye JA, Jick H. )BUT the authors considered ONLY 2 first years of age. My celiac son was diagnosed at 3y 2 months and he never had diarrhea or GI issues during his 2 first years of life. Horvath manuscript presents data on children with 5.7 + or – 2 years.

* It seems that near 10-20 % of the general population has IBS.
Considering all the gastrointestinal problems, children with autism- (age range 0-8 years) has 38 to 60 % maximum diarrhea and near 36 % constipation problems.

A recent manuscript on the issue confirm a high percentage
Biol Psychiatry. 2007 Feb 15;61(4):492-497. Epub 2007 Jan 3.
Relationship of Dietary Intake to Gastrointestinal Symptoms in Children with Autistic Spectrum Disorders.Levy SE, Souders MC, Ittenbach RF, Giarelli E, Mulberg AE, Pinto-Martin JA.
“Reported frequency of GI abnormalities, including abnormal stool consistency (e.g., bulky or loose), was increased (54%)”
These data say that autistic children have near 3 times more GI issues than non- autistic children- for now (20 vs 60 %).

2-Autistic children/teens/adults with gastrointestinal problems have the same symptoms and severity of non-ASD children with the same medical problem-considering other factors such as stress ALSO?

This work compares autistic individuals and non-autistic individuals with different Gastrointestinal issues
Disaccharidase activities in 308 autistic (AI) and 206 non-autistic individuals (NAI) with different GIP (gastrointestinal problems).
The frequency of GIP among AI and NAI was: diarrhea, 38 vs 18 %; abdominal pain, 36 vs 59 %; food sensitivity, 14 vs 11%; constipation, 4 vs. 0.5%; GER (reflux), 3 vs. 11%; FTT (failure to thrive), 2 vs. 6%; diarrhea with abdominal pain, 6 vs 5%; diarrhea with food sensitivity, 6 vs 3%; and abdominal pain with food sensitivity, 4 vs 3%. AI with diarrhea (n = 206) demonstrated significantly lower maltase (P < 0.05) activity than NAI with diarrhea. Frequency of lactase deficiency in AI with FTT (n = 5) was significantly higher (80% vs 25%; P < 0.05) than in NAI with FTT and frequency of palatinase deficiency in AI with diarrhea was significantly higher than in NAI (28% vs 11%; P < 0.05) with the same GIP. AI and NAI with other GIP had similar frequency of disaccharidase deficiencies.
This study presents results on constipation
Although constipation occurs in 2% to 5% of healthy children, its clinical diagnosis is often difficult in children with behavioral disorders. Despite this, moderate or severe constipation was more frequent in the autistic group than in the control subjects (36% vs 10%). 54.4% of autistic children had moderate/severe loading or acquired megarectum compared with 24.1% of control subjects. Milk was the strongest predictor of constipation in the autistic group, whereas stool frequency, gluten consumption, soiling, and abdominal pain were not predictive of constipation (Dr Heuschkel / Dr Afzal publication).

*Diarrhea was present in 38 vs 18%; Lactase deficiency in Autistics with failure to thrive was VERY much higher 80% vs 25 % and palatinase deficiency 28 vs 11 %.
*It seems from these results that milk intolerance ( through lactose, casein intolerance) was related with constipation and enzyme deficiencies –lactase, maltase and palatinase- with diarrhea

The prevalence of IBS in North America is 10-15 % equally divided among IBS with constipation, IBS with diarrhea and IBS alternating between diarrhea and constipation (that is near 3.33 to 5 % of the general population for each). There are 9 population studies and the prevalence varied between 3 to 20 % but most estimates were concentrated between 10 and 15 %. However, these studies´s quality and quantity are limited.

Patients with IBS symptoms have been studied by different tests. In general Colitis IBD, Colorectal cancer, celiac disease, gastrointestinal infection, thyroid malfunction and lactose malabsorption are found. The main difference bewteen the general population and IBS patients is celiac disease (4.67 % vs 0.25 – 0.5 %), being the others in the same range. IBS patients exhibit visceral hypersensivity. Finally behavioral therapy seems to be more effective than placebo at relieving individual IBS symptoms, however no trial has provided unequivocal evidence that psychological treatment is efficacious in IBS.
Then,let´s go to see celiac disease as a form of gluten intolerance. A modern view would focus on gluten intolerance, a very much wider spectrum of problems with gluten
Increasing numbers of atypical or asymptomatic cases of celiac disease are being diagnosed. Celiac disease and cow's milk protein allergy are key examples of chronic enteropathy.

The dietary approach to allergy has evolved to include active stimulation of the immature immune system in order to support the establishment of tolerance.


Nestle Nutr Workshop Ser Pediatr Program. 2007;(59):115-31. Links
Chronic enteropathy and feeding.Salvatore S, Hauser B, Vandenplas Y.
Curr Opin Gastroenterol. 2007 Mar;23(2):142-8.
Advances in celiac disease.Craig D, Robins G, Howdle PD.
Academic Medical Unit, Leeds Institute of Molecular Medicine, Leeds, UK.

Although celiac disease is predicted by screening studies to affect approximately 1% of the population of the United States and is seen both in children and in adults, 10%-15% or fewer of these individuals have been diagnosed and treated.

J Clin Invest. 2007 Jan;117(1):41-9. Links
Celiac disease: pathogenesis of a model immunogenetic disease.
Kagnoff MF.
Celiac disease: pathogenesis of a model immunogenetic disease
And Gluten sensitivity as a neurological illness Hadjivassiliou M, Grunewald RA, Davies-Jones G in Journal of Neurology Neurosurgery and Psychiatry 2002;72:560-563
Where the authors say
“Gluten sensitivity can be primarily and at times exclusively a neurological disease. The absence of an enteropathy should not preclude patients from treatment with a gluten-free diet… Antigliadin antibodies are also found in the CSF… This inflammation was primarily seen in the white matter of the cerebellum. There was also marked but patchy Purkinje cell loss. We have also found antibodies against Purkinje cells in patients with gluten ataxia. Our research suggests that IgG antigliadin antibodies cross react with epitopes on Purkinje cells from human cerebellum… Characterisation of the anti-Purkinje cell antibodies by immunoblotting may provide a useful marker for the diagnosis of gluten ataxia in a manner analogous to the use of antiendomysium antibodies as a marker for coeliac disease or the anti-Yo antibody in paraneoplastic cerebellar degeneration.”
Other authors include conclusions like this
“Celiac disease should be considered in patients with idiopathic neuropathy even when gastrointestinal symptoms are absent”.(Muscle Nerve. 2007 Jan 16; Celiac disease presenting with motor neuropathy: Effect of gluten free-diet.Rigamonti A, Magi S, Venturini E, Morandi L, Ciano C, Lauria G).
Well, now, let´s go to see gut flora differences and other published clues about
* Presence of Clostridia hystoliticum was one of the main findings in FS of autistic chidlren
*Children with autism had 9 species of Clostridium not found in controls, whereas controls yielded only 3 species not found in children with autism.
*Analysis of the real-time PCR data indicated that the cell count differences between autistic and control children for C. bolteae and the following Clostridium groups were statistically significant: mean counts of C. bolteae and clusters I and XI in autistic children were 46-fold (P = 0.01), 9.0-fold (P = 0.014), and 3.5-fold (P = 0.004) greater than those in control children, respectively,
*There is a profile of composition of the intestinal flora that changes with age and development in non-autistic children:
*Healthy children can have chlostridia infections present but they are solved with development –after the year of age-and controlled with the maturation of the immune system. It seems that this change in the immune system has no place in some autistic children, that maintain unhealthy levels of abnormal bacteria in gut and who are affected differently by them.
* Positive presence of fungus of Candida strain in stool in some autistic children is related- many times- to IgA deficiency. Only immunedepressed people present this kind of fungal infections out of control
* Other bacterial infections (Giardasis Escherichia coli ,Blastocytis hominis, staphylococcus aureus amebiasis, parasites) are present under testing-anecdotal evidence [Blastocystis hominis and bowel diseases.]
In vitro growth control of selected pathogens by Lactobacillus acidophilus- and Lactobacillus casei-fermented milk
Bacterial infections of the gut (excluding enteric fever)
Luminal host-defense mechanisms against invasive amebiasis
The bacterial weaponry: lessons from Shigella


This is a free chapter of an immunology book-from the web. It explains very graphically what happens with gut pathogen infections and mucosa gut integrity- with other explanations about adaptive immunity.

Chapter 10


Apparently, very specific kinds of food allergies or intolerances- different things- (non- necessarily IgE mediated or presented as celiac disease as such in the case of gluten), inflammatory gastrointestinal conditions- of several kinds-,alterations of gut flora and overgrowth of certain fungal/bacterian infections would be present in some subgroups of autistic children- generally in combination. This kind of situation in combination are found only in immunedepressed people and in some IBS complicated patients (or transplanted).

3-How does the treatment of GI issues changes the IQ and child´s adaptative behavior with certain recorded changes in biochemistry-metabolism? Anecdotical and published evidence.
There are plenty of anecdotes about the GFCF diet- without clinical correlates. Also, there are plenty of anecdotes with important changes in behaviors upon the treatment of GI issues that provoke disconfort, pain, malabsorption and nutritional imbalances. There are also anecdotes of no effect of a diet GFCF ALONE, especially if there is not concomitant search for potential concomitant medical problems to –if present- gastrointestinal issues ( from reflux to nutritional imbalances). And There are also anecdotes of no effect of the GFCF diet, even with a lot of treatments concomitant to these diagnosis. In some other cases, disaccharidases can be imbalanced and the SCDiet has shown to produce some help. Otherwise, when oxalates are high the oxalate-free diet also has provided some help. And in other cases ketogenic diet has produced positive effects. There is probably no field as changing and challenging as the individual detections of GI issues and the concomitant tretament of TROUGH dietary changes.
Because the problems are presented in combination (Gut flora alterations, presence of abnormal bacteria, food intolerances and nutritional imbalances-related to immune alterations, lack of several enzymes, high level of certain compounds related to malabsorption or biochemical alterations) the research of the treatment should be integral, considering all the aspects TOGETHER. I know that this is a nightmare for controls, but it is the problem many parents must face- and very few researchers consider as such (recent work of Elder et al is a demonstration of my point). The needed incorporation of ambiguety and individuality is not easy from the scientific point of view. However, in my anecdotical experience, it has been important to consider.
Why the GFCF diet is going to produce some change if a child has not a food intolerance to gluten and/or casein? You need testing for this- and there are many test available in current labs.
Why the GFCF diet is going to be tested WITHOUT gut support in the form of probiotics and fungal/bacterian/other testing, diagnosis and treatment? In my anecdotical experience, diet is a tiny part of the overall problem- although it helps.
Why the GFCF diet is going to have some kind of effect in celiac, lactose defficient, enzyme defficient children if the enzymes are not tested, the lactose defficiency is not tested, the nutritional imbalances are not balanced (vitamins, essential elements, minerals, fatty acids- recently present in the news- probably related to lipase defficiencies) and the OTHER gut problems are not treated?
Why almost no researchers take all this into consideration, rendering useless in many cases their findings?
An autistic or non-autistic child with celiac disease, milk intolerance, fungal /bacterian infections in gut, enzyme and nutritional defficiencies, Why avoidance of ONLY gluten and casein si going to show improvement if there are many other problems ALSO that remain undetected/untreated?

O no! again I begun in the basement (gastrointestinal problems) and ended in the living room (the immune system). Well there is an excellent recently published paper- beyond the one on the MET signaling in autism- relating the gut with the immune system that I think it will be interesting to analyze together with the NK, CD8, IgG and IgA…Next time :)

2 Comments:

  • At 1:40 PM, Anonymous passionlessDrone said…

    Hi Maria Lujan -

    You might also be interested in this study, which I recently found.

    http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16685179

    -pD

     
  • At 8:30 PM, Blogger María Luján said…

    passionlessdrone
    Thank you very much for the link.

     

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