Event Overview

  • The Gastrointestinal Metabolome in Clinical Practice- Influence on Mitochondrial Function, Oxidative Stress and Detoxification.

    The role of the complex community of microbial dwellers inside our digestive tract remains a valuable, but still poorly understood resource in which changes to density and variety can have significant effects on human function and health. One of the roles of these organisms is in the generation of endogenous defence molecules including the master antioxidant, glutathione.

    The synthesis of glutathione in each cell in our body is an important rate limiting step in the progression of cellular damage and its role in human health is well recognized. Challenges to its production and utilization include genetic abnormalities such as methylation and histone deacetylase activity, the production of key intermediates, and, diet including consumption of suitable fermentable fibres and digestible proteins.  Additionally, infections, heavy metals, medications and others not only alter glutathione synthesis but create increased demands for it through the induction of pro-inflammatory molecules. It has been recently shown that non-genetic loss of formation of the glutathione-producing enzymes can decrease glutathione and is associated with several health conditions.

    This one day event is designed to explore some of the clinically relevant evolving events in microbiology, mucosal immunity and functional medicine as it relates to inflammation and health. The presenters are well known for their many years of work in research, analysis, practice and lecturing. They will present substantive evidence of these evolving trends and how they impact on clinical decisions, describing where evidence is preliminary, novel, or of greater substantiation. The day will have a strong clinical bias and provide a welcome opportunity for questions and answers.

    The presenters will:

    • Stimulate new ideas
    • Reinforce current best practice methods
    • Challenge entrenched beliefs with evolving comprehension
    • Offer new and substantive clinical ideas
    • Support the functional medicine approach to patient care
    • Diminish the temptation to be protocol driven in treatment plans
    • Provoke discussion and review
    • Provide networking opportunities
    • Make you feel positive about the opportunities for helping more people recover their health safely

     

    Michael Ash DO, ND, BSc, RNT

    A number of contemporaneous studies have highlighted the importance of the gut microbiota for human health through the regulation of host immune response and energetic metabolism. Microbiota it is becoming clear, interact with host cells in particular by modulating the mitochondrial activities. This mitochondria – microbiota cross-talk is of interest because mitochondria and bacteria share numerous common structural and functional features. Recently a range of studies have exposed a strong association between microbiota quality and diversity and mitochondrial function.

    The mitochondrial production of Reactive Oxygen Species does of course play an important role during the innate immune response and inflammation and is often targeted by pathogenic bacteria. The gut epithelial barrier homeostasis is regulated by microbiota through the production of mitochondrial ROS amongst a range of other factors.

    In addition, microbiota released metabolites can directly interfere with mitochondrial respiratory chain and ATP production. Some of them, particularly Short Chain Fatty Acids (SCFAs) have beneficial effects on mitochondrial activity, gene transcription and immune homeostasis. All these data suggest that microbiota target mitochondria to regulate its interaction with the host. Imbalance of this cross-talk may results in pathogenic state as observed in many common non communicable illnesses. Strategies to modulate the quality and diversity of microbiota, improve metabolite induction, and associated microbial capabilities, mediate mitochondrial fitness and competence, improvement in transcription expression and metabolic and metabolite management will be explored as clinical methods for multiple intervention approaches. Food, food concentrates and related molecular pathways will be explored and discussed in context.
     

    David Quig PhD, MS, BS

    A considerable amount of research has moved beyond trying to define the human GI microbiome to identification of core ecological functions that many microbes can perform. The GI metabolome entails a complex network of interactions among and between microbes, and their environment. The environment (terrain) is a complex ecosystem referred to as the intestinal barrier, that includes resident microbial guilds, resident and recruited immune cells, antimicrobial entities, and it’s very own glycobiome. The GI glycobiome includes variably glycosylated proteins (mucins) and lipids that provide a first wave of protective barriers.

    Specific membrane-bound mucins impart selective microbial adhesion that in turn affects microbe-induced alterations in mucin and mucus production and metabolism, and molecular signaling and communication with the host. As such the protective mucus barrier and the glycocalyx provide barriers and surveillance for the underlying epithelial barrier.

    Dysregulation of the glycan-rich and the epithelial barriers contribute to insufficiency dysbiosis that can adversely affect systemic innate detoxification processes that can result in excessive systemic oxidative stress and inflammation. A greater appreciation of the supramucosal barrier can lead to more comprehensive clinical intervention for GI issues and compromised innate detoxification. Definitive ways to assess increased permeability of the epithelial cell barrier, including that induced by gluten, will also be discussed.
     

    Tim Guilford MD

    Every cell in our body, including gastrointestinal cells require the production and utilization of glutathione. Some animal studies have clearly shown that lipopolysaccharide (also known as llipoglycans and endotoxins) exposure in the gut increases free radicals, and oxidative stress and decreases glutathione related functions. Mitochondrial function is dependent on the presence of glutathione to help lessen damage from free radicals formed in the production of energy in our cells. Studies of loss of glutathione in intestinal cells show an increase in lipid peroxidation reflected by malondialdehyde overproduction and reduced antioxidant defense. Loss of glutathione is also associated with increased pro-inflammatory cytokines.

    Clinicians know and understand that the methylation cycle is important for producing an important amino acid needed for the production of glutathione and a lot of emphasis has been placed on the genetics of this pathway. However, it has been shown that the presence of the building blocks of glutathione (cysteine, glutamic acid and glycine) may not ensure the production of glutathione, especially in conditions of oxidation stress and inflammation in cells. For example, the expression of the enzymes needed to put the 3 amino acids together to form glutathione can be decreased by a variety of factors in a number of conditions including HIV, T2DM, mycotoxin related illness and autoimmune disease. In these conditions, it has been shown that the genes for these enzymes are present, but the enzymes are not being formed.

    Using clinical contexts highlighting the pathway for formation of glutathione the presentations will show how blocks in glutathione formation can be bypassed by liposomal glutathione and normal mechanisms restored. The impact of low glutathione on immune cell function and defense against infection will also be discussed in relation to gastrointestinal and metabolomics dysbiosis and dysfunctions.
     

    Who should attend?

    This course is designed for physicians and health care providers who seek to improve GI health and function in their patient population.

© 2016 Nutri-Link Ltd

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