Gastrointestinal therapies for augmenting treatment of autism spectrum disorder behaviors

Hasan Sumdani

Introduction. Autism Spectrum Disorder (ASD) is a neurological condition characterized by behavioral changes such as decreased sociality, limited range of interests, and repetitive behaviors. The etiology of ASD has a large genetic component, but environmental causes are being identified and explored more1. ASD is often associated with gastrointestinal (GI) issues such as diarrhea, constipation, bloating, GERD, and more2. GI-related causative agents for autistic behaviors have been posited since ASD individuals are more likely to have a gut flora that is less diverse in comparison to a neurotypical microbiome. Carbohydrate-metabolizing bacteria in particular are diminished3. The ASD microbiome correlates with an increased concentration of short chain fatty acids (SCFAs) which can attach to receptors on immune cells, provoking an inflammatory response that can cause behavioral changes through the neuroimmune axis4. Proposed therapies for unfavorable ASD behaviors include specialized ketogenic diets (low in carbohydrates, high in fat) and microbiota transplant. Methods. In testing the efficacy of a ketogenic diet, 18 children were psychiatrically evaluated before and after 6 months of diet modification. Children alternated between 4 weeks of diet modification and 2 weeks of being diet-free until 6 months were reached. Diet modification included 71% derivation of calories from fats, 19% from carbohydrates, and 10% from proteins5. In another experiment, microbiota transplants were done on 18 ASD individuals after 14-day vancomycin and a bowel cleanse. A high loading dose of microbiota was administered, with daily maintenance doses for the following 8 weeks. Observation was continued for 8 weeks after treatment was stopped6. Results. All 18 ASD individuals scored lower on the Childhood Autism Rating Scale after adherence to a ketogenic diet. Of a maximum score of 60, 8 individuals showed 2-8 point reduction, 8 individuals showed 8-12 point reduction, and 2 individuals showed greater than 12 point reduction5. Microbiota transplants in 18 ASD individuals restored carbohydrate-metabolizing bacteria that were previously deficient including species of Bifidobacteria, Desulfovibrio, and Prevotella. These bacteria were persistent in the gut for 8 weeks after transplants were stopped, and recipients had up to 80% reduction in GI issues and significant reduction in unfavorable ASD behavior patterns which both also lasted 8 weeks after transplants were stopped6. Conclusions. A combination of treatments including diet modification and microbiota transplantation is likely to be most efficacious in treating unfavorable ASD behaviors and GI disturbances by restoring the biodiversity of the gut flora, imposing less metabolic stress, and preventing neuroimmune responses.

  1. Castro, Kamila, et al. “Effect of a ketogenic diet on autism spectrum disorder: A systematic review.”Research in Autism Spectrum Disorders 20 (2015): 31-38.
  2. Krajmalnik-Brown R, Lozupone C, Kang D, Adams J. Gut bacteria in children with autism spectrum disorders: challenges and promise of studying how a complex community influences a complex disease. Microbial Ecology In Health And Disease. March 12, 2015;26:26914. Available from: MEDLINE Complete, Ipswich, MA.
  3. Kang D, Park J, Krajmalnik-Brown R, et al. Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children. Plos One. n.d.;8(7)
  4. MacFabe, Derrick F., et al. “Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: relevance to autism spectrum disorder.” Behavioral brain research 217.1 (2011): 47-54.
  5. Evangeliou, A., Vlachonikolis, I., Mihailidou, H., Spilioti, M., Skarpalezou, A., Makaronas, N., Smeitink, J. (2003). Application of a ketogenic diet in children with autistic behavior: pilot study. Journal of Child Neurology, 18, 113.
  6. Dae-Wook Kang, Adams, J. B., Gregory, A. C., Borody, T., Chittick, L., Fasano, A., Caporaso, J. G. (2017). Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome