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
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RISK?
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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