Autism, leaky gut and elimination diets

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Autism: Is it linked to leaky gut syndrome? Do elimination diets help?

There has been a lot of “buzz” about the role of increased intestinal permeability (intestinal hyperpermeability) or leaky gut syndrome in the pathogenesis of autism and autistic spectrum disorders or ASD. A leaky gut may allow absorption of larger molecules especially peptides etc. derived from food which then in turn could potentially affect the neurological function manifesting as behavioral problems.

Let’s look at some of the facts:

• Celiac disease that is related to gluten may present with clinical picture of autism.   
• D’Eufemia et al from La Sapienza University in Italy performed a lactulose-mannitol test to evaluate the intestinal permeability in 21 autistic and 40 control kids. The investigators reported that abnormal permeability through a damaged or dysfunctional gut (i.e.leaky gut) was present in 43% of the autistic kids and none of the control children. 
• De Magistris and colleagues from the Second University of Naples, Italy studied alterations in intestinal permeability in kids with autism and their first degree relatives. Abnormal permeability or leaky gut was seen in 37% of kids with autism, as compared to 21% in first degree relatives and only 5% in healthy controls. Faecal calprotectin was increased in 24% of autistic kids, 12% of first degree relatives and none in controls. The investigators concluded that the results support the “leaky gut” hypothesis and measurement of intestinal permeability may identify those kids with autism that  may benefit from elimination diet. In addition, the high prevalence of abnormalities in the relatives indicates that genetic factors involving tight junctions may play a role in the pathogenesis. 
• American Academy of Pediatrics feels that the literature supporting the role of leaky gut in autism is “limited” and that more studies are needed.

If leaky gut plays a role in autism, exclusion of certain foods like gluten and casein with potentially noxious products may help the patients.

• Knivsberg et al. from the Stavanger University College, Norway conducted a randomized controlled trial of effect of gluten free, casein-free diet in kids with autism and found that development of children at the end of 12-months who underwent dietary intervention with gluten-free, casein-free diet was superior to the controls who were on their usual diet. 
• Elder eta l from the University of Florida conducted a double blind cross over trial of casein free, gluten free diet in kids with autistic spectrum disorder. Outcome parameters include autistic symptoms and urinary peptide levels. Overall, there were no differences between the two groups. However, parents of 9 of the 15 kids wanted to continue the diet and reported subjective clinical improvement. 
• A Cochrane database review by Millward and colleagues from the Derbyshire Children’s Hospital in Derby, UK and Literature and Evidence Research Unit at Nottinghamshire Healthcare Trust in Woodbeck, UK conducted a systematic review and meta-analysis of literature on the role of elimination diets in autistic spectrum disorder. The authors identified two randomized controlled trials albeit small. Elimination diet showed benefit in overall autistic traits, social isolation and overall ability to interact. 
• Rossingnol from the International Child Development Resource Center, Melbourne, FL in 2009 gave a grade C recommendation for the use of elimination diets in autistic kids. 
• Since the publication of the above reports, opinions as well as the position statement of American Academy of Pediatrics, another randomized controlled trial has been published. Whiteley et al. from the University of Sutherland in the United Kingdom conducted a 2-stage single blinded randomized controlled trial of gluten free and casein free diet in kids with ASD. Outcome measures included Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) as markers for  core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to evaluate the developmental level, along with nd Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) for assessment of  inattention and hyperactivity. Results at 12-months demonstrated a significant improvement in the intervention group on the  ADOS, GARS and ADHD-IV. Results at 24 months showed benefit was sustained at 24 months although the clinical impact showed a plateau.


Bottom-line: While there is controversy, my "belief" is consistent with Reichelt and Knivsberg from the Rikshospitalet Medical Centre, University of Oslo in Norway who conclude in Annals of Clinical Psychiatry that a gut-to-brain axis connection in autism is both possible and probable based on the effect of diet on excreted compounds and behavior in conjunction with the clinical data available. Obviously, large studies over time will be needed to resolve the controversy.

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Other topics of interest:

1. Can probiotics strengthen selective intestinal barrier? http://goo.gl/cXmry
2. Autism related to gut bacteria? http://goo.gl/omTSd

Autism treatment strategies at the 12-point treatment program for autism.

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