The Kilee Patchell-Evans Autism Research Group
January 22, 2013
American-Canadian collaborative study shows biomarker for abnormal energy metabolism in autistic patients that may result in potential blood test
Results of a recent clinical study by Drs. Richard Frye and Stepan Melynk of Arkansas Children’s Hospital Research Institute in Little Rock, Arkansas and Dr. Derrick MacFabe of the University of Western Ontario, in London, Canada have shown the presence of a unique blood marker suggestive of abnormal energy metabolism in a large subgroup of autistic patients. Moreover, this subgroup of children with autism demonstrates abnormalities similar to those reported in an animal model of autism. This animal model has shown that these metabolic abnormalities may arise, not from genetic factors, but from compounds produced by certain types of bacterial species often found to be increased in the gut of persons with autism.
The paper, entitled “Unique acyl-carnitine profiles are potential biomarkers of acquired mitochondrial disease in autism spectrum disorders”, was recently published in the prestigious peer reviewed open access journal Translational Psychiatry. The study may further the understanding about possible gut linked environmental contributors to autism, and forecast potential blood tests for early screening to identify children with autism.
Autism spectrum disorders (ASD) are a family of developmental conditions of impaired language and social development as well as repetitive behaviors and restricted interests. ASD affects up to 1 in 88 individuals, and the number appears to be increasing. Recent evidence suggests that biological abnormalities in many persons with ASD are not restricted to the brain but can involve other body systems including the immune, energy generation, detoxification and digestive systems.
Problems in overall cellular energy metabolism, particularly involving mitochondria, the energy producers in all cells, have been found in a large number of ASD patients. Impairments in mitochondrial energy metabolism may explain why many body systems are affected in ASD, particularly the brain and gut, which both have high energy demands. Mitochondria also play a major role in fat metabolism, particularly important in brain development and function.
In addition, in recent years, abnormalities of the digestive system have become particularly interesting as it has been recognized that many children with ASD have gastrointestinal symptoms, and many parents report behavioral improvements with special diets. Furthermore, researchers have identified evidence of unique intestinal bacteria in children with ASD. The connection between the gut and the brain has been a mystery, but this new research may shed some light on this important connection and how if may be involved in ASD.
Dr. Frye is the Director of Autism Research at Arkansas Children’s Hospital Research Institute and an expert in metabolic disorders in ASD. In a recent review in Molecular Psychiatry, Dr Frye and his colleague found that many patients with ASD have evidence of abnormal mitochondrial function. However genetic (i.e. inherited) causes for these abnormalities in mitochondrial energy metabolism were comparatively rare, suggesting these metabolic impairments may stem partly from environmental agents, and not solely genetic factors.
In a recent review in Microbial Ecology in Health and Disease, Dr. MacFabe, Director of the Kilee Patchell-Evans Autism Research Group at the University of Western Ontario, has shown in a series of studies that metabolic products from gut bacteria may be potential agents that link abnormalities of the gastrointestinal system with other metabolic and brain abnormalities found in children with ASD. His group found that exposing rodents to propionic acid (PPA), a compound produced by ASD associated gut bacteria and elevated in the stools of autistic patients, produced many striking ASD-like effects, such as bouts of repetitive behavior, decreased social interactions, seizures, and immune and metabolic changes in the brain, including specific abnormalities in mitochondrial metabolism. This animal model is interesting as it allows agents that potentially cause ASD to be studied in a controlled and ethical manner.
In this study of 213 children, the team found 17% of children with ASD had a unique pattern of blood markers of fat metabolism, called acyl-carnitines, as well as other evidence of abnormal cellular metabolism (i.e. reduced glutathione), all consistent and predicted from findings with the PPA rodent model. This study suggests that ASD in some patients can arise from alterations in mitochondrial function and fat metabolism following environmental exposure to PPA produced from ASD associated gut bacteria. It found that many of the metabolic markers found in the ASD patients could be explained by PPA interfering with mitochondrial metabolism, and warrant further study, both in the animal model, and then in patients. The study also notes many potential genetic and acquired factors, including antibiotics, dietary carbohydrates, gut disorders and inherited abnormalities of fatty acid metabolism, all reported in ASD, that could further contribute increased risk to acquiring ASD through interfering with mitochondrial function and the production or break down of PPA and related gut fatty acids.
This study may be important as it allows the ethical development of potential biomarkers (acyl-carnitine profiles) to identify and screen ASD patients or even those “at risk” of developing ASD before ASD symptoms manifest. It also furthers the understanding of how ASD or ASD symptoms may develop or fluctuate. It offers a potential explanation of how mitochondrial dysfunction may play in ASD, and allows ethical understanding of how potential treatments, such carnitine supplementation, which aids mitochondrial function, may be of benefit to some patients with ASD, or to possibly prevent ASD in infants who would show the unique acylcarnitine profile. It also provides further evidence of environmental agents, particularly those arising from diet or the digestive tract as potential contributors to some types of ASD.
This Canadian multi-disciplinary team is located at the University of Western Ontario in London, Ontario and led by director Dr. Derrick MacFabe. The research team is a group of like-minded biomedical researchers from various fields reflecting the diverse aspects of this family of disorders. This research group is examining the effects of a number of dietary and digestive system compounds on brain development, function, and behaviour. The researchers have found that these compounds, in an animal model, produce the repetitive and social behavioural and brain inflammatory changes resembling many aspects of human Autism Spectrum Disorders. This research to date is providing a highly important framework for the possible linkage of genetic, immune, digestion and dietary factors in autism. Click here to visit The Kilee Patchell-Evans Autism Research Group's Website.