Thursday, June 26, 2014 (Speaker's times and presentation aims may be subject to change but will include talks on the microbome with possible relevance to Autism)
Introductions / Discuss Goals
Dr. Tore Midtvedt, Karolinska Institute. Presentation: The Gut and the Brain:
A Scandinavian way of approaching autism
The burning question in autism research today is how to unmask the patho-physiological mechanisms behind development of autism in a child.In cooperative studies between groups at the Karolinska Institute, Stockholm, Sweden, the National Institute of Health, Oslo Norway, Oslo University and Bergen University, Norway, we are a) closely following the establishment of a gut microbiotoa in a large cohort of newborns – microbiologically as well as biochemically – for some years after birth bb) monitoring interactions between dietary factor and behavior; and c) by magnetic resonance spectroscopy comparing amounts of some specific biologically active components in selected brain areas in autism and control children.
The lecture will be focused upon some microbial components along this road.
Dr. Carl Cerneglia, National Center for Toxicological Research. Presentation: Microbiome and the Environment.
The human gastrointestinal tract ecosystem consists of complex microbial communities that play an important role in maintaining and influencing human health. The use of veterinary antimicrobial agents in food-producing animals may result in the presence of drug residues in edible foodstuffs that may pose a risk to human health by increasing the rate at which antimicrobial resistance occurs to clinically significant antibiotics. Therapeutic doses of antibiotics have been known to shift the microbiome in the gastrointestinal tract and these disruptions contribute to exacerbation of disease and promote the emergence of antibiotic resistant bacteria. However, less is known about the impact of lower-level concentrations of antimicrobial agents in the human food supply than that of therapeutic doses on public health with regard to the effects of ingested residues on the human intestinal microbiome. To address these human food safety concerns, scientists in the Division of Microbiology /NCTR have conducted state–of–the–art research that addresses pivotal questions raised by national regulatory authorities and scientific advisory groups about the potential impact of drug residues, in foods derived from animals treated with antimicrobial agents, on the human intestinal microbiota. Specifically, do drug residues entering the colon remain microbiologically active, and if so, do they alter the composition of the human intestinal microbial community and increase the population of drug-resistant bacteria? This significant research has provided data, scientific methodology and general recommendations to the FDA and other national regulatory authorities on drug inactivation, bioavailability, drug metabolism, and antimicrobial resistance to improve the safety evaluation and risk assessment of the impact of antimicrobial residues on the gastrointestinal microbiota to ensure food safety.
Break - Coffee
Dr. Emma Allen-Vercoe, University of Guelph. Presentation: The human gut microbiota: forgotten organ, important ally.
We are all colonized with trillions of microbes that are increasingly being shown to have great importance in the maintenance of health. Modern human practices, including antibiotic use, increased sanitation, C-section birth and formula feeding have been shown to exact a price on our microbial symbionts, to the extent that it has been recently postulated that some of these microbes may be becoming extinct. In this talk I will explain how this ecosystem loss may lead to disease and will illustrate this in the context of Clostridium difficile infection, a very clear case of disease resulting from gut microbial ecosystem damage. I will also indicate how gut microbial ecosystem damage might be of relevance in autism. Finally, I will outline some of the pioneering work we have initiated to create therapeutic strategies for gut microbial ecosystem correction.
Dr. Derrick MacFabe University of Western Ontario. Presentation: Gut Bacterial Metabolites as Possible Environmental Triggers of Autism Spectrum Disorder
From Animal Models to Human Populations Clinical observations suggest that gut and dietary factors, transiently worsen, and in some cases appear to improve, symptoms in autism spectrum disorders (ASDs). Recent evidence suggests ASD as a family of systemic disorders of altered immunity, metabolism and gene expression. Pre or perinatal infection is emerging as a major risk factor for ASD. Can a common environmental agent link these disparate findings? This lecture outlines basic science and clinical evidence that short chain fatty acids, present in diet and produced by opportunistic gut bacteria following carbohydrate ingestion, may be key triggers in ASD. Dr. MacFabe presents his current research examining propionic acid, a major fermentation product associated with opportunistic ASD associated gastrointestinal bacteria, and its ability to produce reversible behavioral, electrographic, neuroinflammatory, metabolic and epigenetic changes closely resembling those found in ASDs. It discusses the hypothesis that ASDs are produced by pre or post-natal antibiotic resistant bacterial infections in sensitive sub populations, which may have major implications in ASD cause, diagnosis and treatment.
Dr. Jim Adams and Dr. Rosa Krajmalnik-Brown, Arizona State University. Presentation: Gut Bacteria in Children with Autism.
We have conducted two pilot studies of gut bacteria in children with autism, with both studies finding that children with autism have about 25% less types of bacteria than found in typical children. We also found particularly low levels of one type of bacteria, Prevotella. We also investigated metabolites from gut bacteria and found several abnormalities, with most related to neurotransmitter precursors or degradation products. Finally, we will briefly discuss the implications of these findings in terms of possible treatments, with a focus on fecal transplants.
Lunch (Lunch Provided to 1st 50 registered attendees).
Dr. Susan Swedo, National Institute of Health. PANDAS/PANS and the Microbiome
Dr. Richard Frye, University of Arkansas for Medical Sciences. Presentation: The Influence of Microbiome Metabolites on Mitochondrial Function in Children with Autism Spectrum Disorder
Autism spectrum disorder (ASD) has been associated with mitochondrial disease and dysfunction. However the etiology of abnormalities in mitochondrial function is unknown as the majority of the cases of mitochondrial disease in children with ASD do not have any obvious link to genetic defects. Recent studies have linked changes in the microbiome to ASD. Enteric bacterial fermentation product such as propionic acid can be produced by gut bacteria that have been associated with ASD such as Clostridia. Short-chain fatty acids, such as propionic acid, can alter mitochondrial function, leading to altered bioenergetics. We have recently demonstrated that some children with ASD and mitochondrial disease have biomarkers of abnormal mitochondrial metabolism that parallel biomarkers previously identified in the propionic acid rodent model of ASD, suggesting that these children may have acquired their mitochondrial disease from changes in the gut microbiome. In this talk I will review some of the links between microbiome metabolites and mitochondrial dysfunction as well as demonstrate the empirical evidence for such metabolites causing mitochondrial disease and dysfunction in children with ASD.
Dr. William Parker, Duke University. Presentation: The (Potential) Role of Fauna and Flora Disruption in the Human Body as Constituents to the Development of Autism
Immune dysfunction is widespread in modern culture, leading to widespread allergy, autoimmunity, and other inflammatory diseases. Evidence now points toward this immune dysfunction as being pivotal in the development of a variety of neurological disorders, including autism. Current evidence suggests that a limited number of cultural factors destabilize immune function in modern society. Primary among these factors is “biome depletion”, or loss of species diversity from the ecosystem of the human body. In this lecture, ongoing studies will be described which examine how the fauna (animal life such as helminths) normally associated with the human biome can modulate immunity, alter the microbiome (microbial flora), and protect brain function and development.