Non-celiac Gluten Sensitivity and

Autism Spectrum Disorders

“Gluten Free for Life”Timothy Buie MD April 11, 2015

Conflict of interest

I am interested in bread, pasta, you name it

I am conflicted as to whether these foods are good for me or others

I have no financial conflicts

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Gluten Concerns and Autism Go Way Back

Autism was described by Leo Kanner in 1943

A compendium of articles including one penned by Asperger (1951) suggested the link of autism behaviors to gluten exposures

Dohan (1961) demonstrated the remarkable increase in exposure to gluten in the diet post World War II and an increase in schizophrenia diagnosis (Autism was characterized as childhood schizophrenia at the time)

Since the 1970’s there are continued publications evaluating diets for autism and prominent among them are milk and gluten free diets

WHERE THERE’S SMOKE…… ???

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Considered Mechanisms

Celiac Disease

Wheat Allergy

Problems with other component of the food such as CHO maldigestion

Dealing with the non-digestible component of gluten

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Celiac and Autism

Early studies did not differentiate Celiac Disease from any other gluten reactions and as you have heard only with the advent of current antibody testing can we attempt to stratify reactions to foods

Pavone (1997) suggested no link in a limited population of children with autism

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Celiac and Autism

Ludvigsson et al (2013) in A Nationwide Study of the Association Between Celiac Disease and the Risk of Autistic Spectrum Disorders reported no higher frequency of celiac identified by intestinal biopsy in patients with ASD over the general population in Sweden

However, there was a higher risk of positive screening markers (IgA/IgG gliadin, endomysium, or tissue transglutaminase) in patients with autism with normal biopsies

Does abnormal antibody response reflect OTHER RISK?

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Wheat Allergy

Current data suggest the prevalence of food allergy in pediatrics to be approximately 5-8%

Food allergy may be 2X more common in boys (Liu 2010)

Eight foods account for 90% of all food-allergic reactions: milk, eggs, peanuts, tree nuts (e.g., walnuts, almonds, cashews, pistachios, pecans), wheat, soy, fish, and shellfish.

Wheat is not in the top 5 food allergens Debate still continues regarding best measures to

establish a supportable diagnosis of allergy: Skin testing, IgE based measures

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Non-Digestibles

Gluten foods have a number of non-digestible components

The protein product itself cannot be completely digested by our digestive capabilities

Lectins which may be gut toxic and are associated with a variety of autoimmune conditions

Phytic Acid may be an anti-nutrient affecting absorption of a number of minerals in the gut

Carbohydrate digestion impairment is rare.

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ASD and Gluten: What problems are we talking about?

It is reasonable to consider the IF gluten is a trigger for GI disturbance, IBS, permeability issues of the gut that have been discussed THEN individuals with autism have equal rights to have those same issues

The difficulty is autism is the clinical presentation

Non-verbal individuals may manifest underlying GI of other medical issues in a behavioral fashion simply because they cannot communicate what is wrong

In autism, the highest correlations of self injurious or aggressive behavior are non-verbal status and the presence of associated GI conditions

Perhaps therefore GI conditions may worsen the “autism behaviors” without necessarily causing autism

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Billy

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Billy

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Could Gluten or Food Sensitivity Cause Autism or Autism Symptoms?

Mechanisms

Opioid peptide theory

Altered intestinal flora

Altered intestinal permeability

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Opioid Peptide Theory

Early speculation linking the foods (milk and gluten) to the presence of urinary peptides that were shown in vitro to bind to opioid receptors

Several reports in selected children with autism where these peptides were identified

Suggestion that increased quantities of these peptides were noted when there was abnormal permeability, including in patients with celiac who did not have autism

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Opioid Peptide Theory

Recent studies seeking to replicate previous findings did not identify these products as more common in autism (Elder et al 2006)

Cass (2008) showed no higher frequency of abnormality in children with autism and that peaks identified as consistent with casomorphin or gliadomorphin were not those substances on confirmatory studies

Many neurotransmitters have been implicated in autism, opioid receptor genetics are normal

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Altered Intestinal Microbiota

Multiple studies in past several years show altered microbiome assessments in children with autism. Our own group with Columbia identified Sutterella (a potential pathogen) in intestinal biopsies of children with autism (Williams 2012), this was not present in unaffected children

Other studies are supporting the presence of excess clostridial species among others in children with autism

Lack of diversity and reduced lactose fermenters are a common report

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Altered Intestinal Microbiota

Diminished presence of B Fragilis in children with autism has been noted and providing B Fragilis in animal model for autism corrected autism features (Hsiao 2013)

Altered microbiota may develop as a result of dietary selectivity or alteration

Altered microbiota likely lead to altered gut metabolome and these bacterial byproducts may alter nervous system communication

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Intestinal Permeability

Altered intestinal permeability has been reported frequently in autism

This may be a result of food reactivity or immune modulation related to foods

A recent study we’ve presented in abstract form did not show that increased permeability issues were noted with greater frequency in our children with autism compared to unaffected comparisons and was not correlated to the inflammation noted by intestinal biopsy performed contiguously.

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Gluten Free Trials

Knivsberg, 1990: Selected patients with high gluten opioid peptides in urine. 8/10 were reported to have behavioral improvements noted. Duplicated study in 2002

Sponheim 1991: Selected 4 children with autism for gluten-free diet, behavior worsened

Whiteley, 1999: Observation study of gluten free diet, 2/3 had behavioral improvements noted

Where else? Unraveling the Mystery of Autism, by Karen Seroussi (Simon and Schuster, N.Y.N.Y. 2000)

Gluten Free Trials

Elder et al* 2006 double-blind crossover trial Casein-free, Gluten-free diet in 15 children with autism showed no benefit of diet in a 12-week study

Blinded parents reported benefits not identified by testing. Perhaps subtle changes/benefits will not be retrieved through standard tests.

Similar trial from Susan Hyman’s group in Rochester reported in abstract form

*J Autism Dev Disord. 2006 Apr;36(3):413-20

Critique on diet trials

Selection

Outcomes

Importance of timing of intervention

Linkage of diet to the alteration of microbiota before and after will be remarkably useful and are not published in this population as of now

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Conclusions

I believe there will be a group of candidate individuals with autism who will have improvement in their GI status, behaviors and perhaps core autism features by gluten =/- other food restriction diets

We have not adequately identified a candidate sub-group to improve likelihood of response

Until such time, individual counseling is needed to determine the potential benefit of this diet or others for the management of autism

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