Derrick MacFabe, MD FACN, Director of the Kilee Patchell-Evans Autism Research Group
Since 2003, Dr. Derrick MacFabe has been Assistant Professor and Director of the Kilee Patchell-Evans Autism Research Group (http://kpearg.com/), Depts. of Psychology (Neuroscience) & Psychiatry (Division of Developmental Disabilities), at the Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. He is also a Core Member of the iTARGET Autism Initiative, University of British Columbia, Vancouver. Dr. MacFabe is currently a Visiting Professor, Centre for Healthy Living and Food Innovation (HEFI), Faculty of Medicine, Maastricht University, Netherlands.
Dr. MacFabe’s research examines the role of the role of gut- microbiome-brain interactions on the identification and possible treatments of autism spectrum disorders. His research examining potential gastrointestinal and infective links in autism has been listed among the “Top 50 Scientific Discoveries in Canada” by the Natural Sciences and Engineering Research Council of Canada and was featured on the Canadian–EU documentary “The Autism Enigma.” He was recently called to speak at the Nobel Conference “The Microbiome and its programming of body systems” held at the Karolinska Institute, Stockholm, Sweden. Dr. MacFabe was awarded the Max Bramer Award from the American Academy of Developmental Medicine and Dentistry and Special Olympics. He was a recent recipient of the Mark Bieber Award from the American College of Nutrition and is a member of their Board of Directors.
Abstract: Enteric Short Chain Fatty Acids: Microbial Messengers of Metabolism, Mitochondria and Mind: Implications in Autism Spectrum Disorders
Clinical observations suggest that gut and dietary factors, transiently worsen, and in some cases appear to improve, symptoms in autism spectrum disorders (ASDs), but the reason of this is unclear. Recent evidence suggests ASD as a family of systemic disorders of increasing incidence manifesting altered immunity, metabolism and gene expression, and altered components of the gut microbiome. Pre or perinatal infection, antibiotics, hospitalization or recent human migration are emerging as a major risk factor for ASD. Can a common environmental agent link these disparate findings? Dr. MacFabe has proposed that short chain fatty acids, represent a group of compounds produced by the host microbiome from dietary carbohydrates can induce widespread effects on gut, brain, and behavior, and link the diverse symptoms and findings in ASDs.
Dr. MacFabe and his collaborative team have found, through basic and translational research and clinical studies, that enteric short chain fatty acids, present in diet and produced by the gut microbiome, particularly by opportunistic gut bacteria following carbohydrate ingestion, may be key triggers in ASD. Propionic acid, a major short chain fatty acid fermentation product associated with ASD associated gastrointestinal bacteria and also a common food preservative, when administration in rodents, elicits behavioral (hyperactive, antisocial, object fixation, perseverative) electrographic (seizure, tics) , neuroinflammatory, metabolic (lipid, mitochondrial, redox, glutathione, acylcarnitine) and epigenetic changes closely resembling those found in ASDs. Similar studies have been found with lymphoblasts from neurotypical and ASD cell lines. Thus, these short chain fatty acids directly or indirectly contribute to acquired mitochondrial and immune dysfunction, and are predictive of novel biomarkers in a large cohort of ASD patients. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut.
Human populations that are partial metabolizers of PPA (organic acidurias, mitochondrial disorder) are more common than previously thought, and thus represent a population “at risk”. PPA has further bioactive effects on neurotransmitter systems, fatty acid metabolism, gap junction gating, immune and mitochondrial function, and gene expression that warrant further exploration. Regarding the latter, the Group have recently found PPA and to a lesser extent butyrate has widespread effects on alteration of gene expression of ASD related genes (neurexins, neuroligins, GABA receptors) and neurodevelopmental, metabolic and immune pathways. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs. Collectively, this research offers further support that gut microbiome metabolites, such as dietary or enteric bacterially produced SCFAs, 1) underappreciated modulators of brain development, function and behavior, 2) may be plausible environmental agents that can trigger ASDs, 3) offer potential novel preventative and therapeutic therapies throughout the lifecycle, and 4)deserve further exploration in basic science, agriculture, and clinical medicine.
Dr. MacFabe’s background includes both basic and clinical neurological sciences. His expertise includes: cellular mechanisms of intra- and intercellular communication, metabolism, inflammation and epigenetics in brain physiology and its implications in stroke, epilepsy, neurodegeneration and neurotrauma as well as neurodevelopmental disorders. He has a particular interest in the role of pre and post natal infectious processes and alterations of the gut microbiome in the etiology and behaviors of autism spectrum disorders. As a Co-Founder and Principal Investigator within the KPEARG, he is actively contributing to the international development of international multi-disciplinary collaborations/technology transfer, novel translational animal models, and clinical studies, on the role of genetics, biochemistry, microbiology and environment on the identification, prevention and possible treatments of autism spectrum disorders. As a recently awarded Fellow and now an elected member of their Board of Directors, Dr. MacFabe and the KPEARG is now partnering with the American College of Nutrition (http://www.americancollegeofnutrition.org/), to promote evidence based interdisciplinary research into dietary/microbiome/metabolism/host interactions in health and disease. Of note, Dr. MacFabe and the College are interfacing with professional schools, basic research, education in broad populations, and also to promote “healthy eating” in persons at risk (pregnancy, infancy, schools, socially disadvantaged groups, newcomers and those with developmental disabilities) and evidence based research in this rapidly developing field.
Compounds produced by gut bacteria alter immune function and energy metabolism in autism
March 12, 2018 (London, Ontario): Two recent papers, one in Translational Psychiatry and another in Frontiers in Immunology by a longstanding Canada-US research collaboration, have found further evidence that compounds produced by bacteria contained in the microbiome, the trillions of bacteria in the digestive tract, have major effects altering the way our bodies function.
These compounds, known as short chain fatty acids, can fine tune our gut, immune system and metabolism. They may even alter our brain function and behaviour and may offer a potential link with the growing incidence and peculiar association of digestive, immune, metabolic and dietary issues, early infections, hospitalizations and microbiome alterations often found in persons with autism spectrum disorders (ASD). (More here)