1. 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

2. 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)

3. 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

4. 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
Neish. Gastroenterology. 2009;136:65-80.
Neish. Gastroenterology. 2009;136:65-80.

5. 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.
4 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
HIV Infection
Fig 1. Dysbiosis, an “imbalance in the structure and/or function of the microbiota that leads to disruption of host-microorganism homeostasis,”6 has been implicated in a broad range of inflammatory disease states. There is also suggestive evidence that changes in gut microbiota have implications for cognitive and mental health dysfunction and stress responses. These diverse multisystem influences have sparked interest in strategies to favorably modulate the gut microbiota to attain homeostasis.
Dysbiosis: an “imbalance in the structure and/or function of the microbiota that leads to disruption of host-microorganism homeostasis”
West CE et al. Journal of Allergy and Clinical Immunology, Volume 135, Issue 1, 2015, 3–13

6. 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
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

7. Dysbiosis in HIV infection
Zevin, McKinnon, Burgener, Klatt; Curr Opinion HIV/AIDS 2016

8. 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.
Marchetti G et al. Clin Micro Rev 2013;26: 2-18.

9. 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