Autism And Celiac Disease

The link between Autism and Celiac disease: Study at a glance

What is Celiac Disease?

Celiac disease (CD) is defined as an autoimmune disease of small intestine, which occurs in genetically predisposed people after the ingestion of gluten. The disease is triggered following intake of gluten, which cross-reacts with immune system thus causing an inflammatory damage to the villi lining the small intestine (area which helps to absorb nutrients). As a result, the disease interferes with the nutrients absorption such as calcium, iron, folate, vitamin D, protein, fat and cause severe vitamin deficiencies. The chemical mechanism behind the immune system response towards gluten is a delayed type hypersensitivity reaction, which perceives a secondary cellular response, usually 48-72 hours after gluten exposure and quite different from immunoglobulin-E (IgE) mediated food allergies. Gluten is a protein component, present in the seeds of cereal grains such as wheat, oat, barley and rye. Due to sensitivity to gluten, the disease is also entitled as gluten-sensitive enteropathy, and gluten intolerance. The disease is sometimes misinterpreted as wheat allergy. However, it is quite different from wheat allergy, since it is caused by reaction to some of the wheat proteins. The only known effective treatment is a lifelong gluten-free diet, which lowers the risk of autoimmune reaction in celiac disease patients.

Neurologic overture of Celiac Disease

The clinical symptoms of celiac disease (CD) vary greatly from one person to another and show a broad range of typical intestinal to atypical extra-intestinal symptoms. The extra-intestinal symptoms potentially affect any organ of body system, including the nervous system. The first clinical report regarding the relationship between the central nervous system and celiac disease came from studies conducted by Cooke and Smith in year 1966. This initial finding was subsequently followed by multiple case reports of patients with established celiac disease and diverse neurological disorders including epilepsy, dementia, cerebellar ataxia, peripheral neuropathy, migraine and depression.

Evidence for a link between Autism and Celiac disease

The relationship between Autism and Celiac disease is poorly understood and conflicting subject over the last several decades. The recurring incidence of gastrointestinal disorders and food intolerances in patients with autism develops a general believe among autism experts about a possible link between celiac disease and autism. Several case studies reported that children with autistic disorders experience chronic constipation and diarrhoea, loose stool, abdominal pain and discomfort. It has been observed that the risk of developing neurological complications in celiac disease patients is higher in children than in adult. This might be due to strict adherence to diet, early exclusion of gluten from diet, short disease span and varied response to immune-mediated disorders. Studies also reported comparable immune-pathologic changes in the intestinal mucosa of autistic and celiac children.

The core concept behind the role of celiac disease in the pathogenesis of autism is principally ground on the implication of gluten and casein sensitivity in autism, also known as leaky-gut theory. This theory suggests that abnormal intestinal mucosa of celiac patients allows excessive absorption of short undigested peptides produced from incomplete digestion of dietary gluten and casein. These short undigested peptides either act as exorphins (opioid peptides, which resembles with opiate chemicals) or elicit an immune response, thus directly influencing the nervous system. The presence of excess peptides or defective peptidase activity from abnormal intestinal mucosa in autism patients further sustains this hypothesis.  It has been observed that gluten and casein restricted diets can ameliorate core and peripheral symptoms of autism and improve developmental outcome (such as changes in areas of attention, communication, and hyperactivity) in autistic patients. A significant positive outcome has been reported following dietary intervention in the majority of published studies. Therefore, dietary intervention such as gluten-free (GF), casein-free (CF), or gluten- and casein-free diet (GFCF) has become attractive in autistic patients.  A case study conducted at University of Alberta, Alberta, Canada showed a rapid improvement in gastrointestinal and autism symptoms following dietary intervention in a boy, which suffered from autism, celiac disease and nutrient deficiencies.

These responses to celiac diets in autistic children propose a possible association between the two diseases, which is primarily based on gluten intolerance and subsequent malabsorption. However, despite these facts, a direct proof of alliance between celiac disease and autism is still lacking. Studies conducted by Lionetti and co-workers at Department of Pediatrics, University of Catania, Italy suggest that it is difficult to digest a correlation between gluten uptake and incidence of central nervous system abnormalities in diseases like autism, which usually begins after the first six months of age. Careful analysis of autistic children histories revealed early onset of disease symptoms, which typically arise well before the age of 18 months. This early onset of disease thus provides a very limited time to consume gluten-containing foods. The presence of altered peptidase activity, urinary peptides and abnormal intestinal mucosa in autism patients are still a controversial issue. Most of the findings have not been replicated and their interpretation remains highly controversial. Studies conducted by researchers to examine possible connections between celiac disease and autism were failure to validate the hypothesis that a link might exist. There is very little evidence that this association really exists and compliance between clinicians and researchers is still lacking.

Scientific view

The major technical limitation of these studies is the age of onset of the celiac disease, which is variable and some of the autistic patients could develop it in the future. This generates heterogeneity of evaluation that interferes with data analysis and interpretation, which prompted professionals to be cautious with such studies. Most of the studies, which support a link between autism and celiac disease or autism and gluten sensitivity, suffered from the lack of direct evidence, statistically demonstrable association, small sample sizes, and methodological shortcomings. Under this situation, it is convincing to accept that the concomitant occurrence of autism and celiac disease in the same individual is purely coincident and improvement in autistic behaviour followed by restricted diets are possibly due to some other unclarified mechanisms. Additional well focussed prospective studies with appropriate control are needed to prove the link between autism, gluten sensitivity and celiac disease. Defining the symptoms and biochemical markers to examine the associated underlying mechanisms of gluten sensitivity and nervous system response is an important area for future investigations. Further, scientific and clinical studies to assess the effect of gluten-free diet and its impact on immuno-modulation of neurological disorder are warranted.

The outcome

The connection between celiac disease and autism is not completely affirmative; however the profusion of positive clinical studies cannot be simply ignored. Some autism experts recommend dietary approaches to the treatment of autism, which most often stimulates a great interest among parents seeking treatment for their children diagnosed with autism. However, it generates disagreement among professionals working in this field. According to them, gluten-free or casein-free diets may produce negative side effects and are ethically debatable. In some autistic children, such a diet showed positive consequences, while in others such diets were poorly tolerated. Therefore, it is advised that such diets could not be applied by parents alone and seems to be the responsibility of professionals and specialized teams in autism.  In conclusion, clinical entities, and accredited medical professionals should acclaim all children with neuro-developmental disorders for food sensitivity and mal-absorption assessment.

 Suggested References

Barcia, G., A. Posar, et al. (2008). “Autism and coeliac disease.” J Autism Dev Disord 38(2): 407-408.

Batista, I. C., L. Gandolfi, et al. (2012). “Autism spectrum disorder and celiac disease: no evidence for a link.” Arq Neuropsiquiatr 70(1): 28-33.

Bushara, K. O. (2005). “Neurologic presentation of celiac disease.” Gastroenterology 128(4 Suppl 1): S92-97.

Fasano, A. and C. Catassi (2012). “Clinical practice. Celiac disease.” N Engl J Med 367(25): 2419-2426.

Genuis, S. J. and T. P. Bouchard (2010). “Celiac disease presenting as autism.” J Child Neurol 25(1): 114-119.

Lionetti, E., R. Francavilla, et al. (2010). “The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta-analysis.” Dev Med Child Neurol 52(8): 700-707.

Martinez-Bermejo, A. and I. Polanco (2002). “[Neuropsychological changes in coeliac disease].” Rev Neurol 34 Suppl 1: S24-33.

Pietzak, M. (2012). “Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad.” JPEN J Parenter Enteral Nutr 36(1 Suppl): 68S-75S.

van Heel, D. A. and J. West (2006). “Recent advances in coeliac disease.” Gut 55(7): 1037-1046.

Zelnik, N., A. Pacht, et al. (2004). “Range of neurologic disorders in patients with celiac disease.” Pediatrics 113(6): 1672-1676.

Some Related Articles:

1. Autism And Diet
2. Vaccines and Autism
3. Autism and Depression
4. Autism and Bad Behavior
5. Autism Vs. Developmental Delay