Transcript PPT - IAS-USA

What’s All the Fuss About the Microbiome?
E. Turner Overton, MD
Associate Professor of Medicine
University of Alabama at Birmingham
Birmingham, Alabama
Washington, DC: August 24, 2016
Financial Relationships With Commercial Entities
 Dr Overton has served as a consultant or
advisor for Bristol-Myers Squibb, Gilead
Sciences, Inc, and Janssen Therapeutics.
(Updated 08/17/16)
Slide 2 of 29
Learning Objectives
After attending this presentation, participants will be
able to:
 Identify mechanisms driving end organ disease in
treated HIV
 Describe the effects of HIV infection on the
intestinal microbiome
 Describe to patients the link between gut
microbiome and a person’s overall health
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What Is The Gut Microbiome, Alex?
 Large, stable community of bacteria
 ~ 100 trillion microbial cells
 ~1,000 bacterial species
 Unique to each individual
 Role in nutrient metabolism, barrier
function & immunity
 Impacted by diet, genes, alcohol,
tobacco, exercise, medications, stress
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Neish. Gastroenterology. 2009;136:65-80.
Neish. Gastroenterology. 2009;136:65-80.
Microbiome Dysbiosis for 200, Alex?
Our forgotten organ
• The bacteria in the microbiome are symbiotic to the human
organism and contribute to health and wellness.
HIV
• 4Infection
predominate bacterial phyla
• Firmicutes
• Bacteroidetes
• Actinobacteria
• Proteobacteria
• Involved in Many processes
• Immune system development
• Digestion and detoxification
• Synthesis of vitamins
• Hydrolysis of indigestible dietary compounds
• Polysaccharides
• Defense against pathogenic bacteria
• Fat storage
• Angiogenesis development
• Behavior
development
Dysbiosis:
an “imbalance in the structure
and/or function of the
microbiota that leads to disruption of host-microorganism homeostasis”
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West CE et al. Journal of Allergy and Clinical Immunology, Volume 135, Issue 1, 2015, 3–13
Dysfunctional Gut-Liver Axis Induces Systemic Inflammation
HIV Infection Induced Changes in the GI Tract
• Depletion of Th17, Th22 CD4 cells
• Dysbiotic intestinal flora
• Increased mucosal permeability
Consequent bacterial translocation via
portal vein
• Activation of Innate Immune System
• Intrahepatic inflammation
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Inflammasome
Activation
•
•
Metabolic Stress
Inflammatory Cytokine Production
Intrahepatic Complications
• Recruitment of Monocytes and Neutrophils
• Activation of Kuppfer Cells
• Fibrogenesis
Systemic Complications
• Pro-inflammatory Lipids
• Insulin Resistance
• Activated Monocytes
Dysbiosis in HIV infection
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Zevin, McKinnon, Burgener, Klatt; Curr Opinion HIV/AIDS 2016
Conclusions
• HIV depletes the CD4 cells, preferentially from the gut
associates lymphoid system.
– This alteration leads to impairment of the gut mucosa integrity.
– This alteration also contributes to intestinal dysbiosis.
• Microbial Translocation subsequently ensues with resultant
systemic inflammation.
• Ultimately, this process leads to excess risk of many non-AIDS
comorbidities.
• Diet and behavioral factors also contribute to this process.
• Studies are ongoing to identify interventions to reverse the
alterations in the GALT, restore the intestinal mucosal health,
and prevent the consequences of excess microbial
translocation.
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Marchetti G et al. Clin Micro Rev 2013;26: 2-18.
What’s All the Fuss About the Microbiome?
E. Turner Overton, MD
Associate Professor of Medicine
University of Alabama at Birmingham
Birmingham, Alabama
Washington, DC: August 24, 2016