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Uncovering the impacts of circumcision on the penis microbiome, Translational Genomics Research Institute (TGen), Lance Price, Copenhagenomics 2012
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Uncovering the impacts of circumcision on the penis microbiome, Translational Genomics Research Institute (TGen), Lance Price, Copenhagenomics 2012

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Dr. Lance Price, Director of Center for Food Microbiology and Environmental Health …

Dr. Lance Price, Director of Center for Food Microbiology and Environmental Health
Translational Genomics Research Institute (TGen) presents his talk: Uncovering the impacts of circumcision on the penis microbiome

Published in: Education, Health & Medicine

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  • Sub-Saharan Africa is home to 67% of all people living with HIVHeterosexual transmission is the most common route of infection in Africa (>90%)
  • Transcript

    • 1. Uncovering the Impacts of Circumcision on the Penis Microbiome Lance B. Price, PhD Director, Center for Microbiomics and Human Health
    • 2. Large of number AIDS-associated deaths:• > 2.0 million people died due to AIDS in 2007.A trend in decreasing number of new infections:• 3.0 million in 2001 to 2.7 million in 2007.• As HIV incidence rate stabilized since 2000, the overall number ofpeople living with HIV has steadily increased. UNAIDS
    • 3. The Rakai Uganda Study• Randomized-controlled trial assessing the effect of male circumcision on risk of HIV seroconversion in adult men – PI: Ron Gray – Enrolled 4,996 healthy, HIV-negative, uncircumcised men, aged 15-49• Randomized into two study arms: – Intervention arm: Immediate circumcision – Control arm: Circumcision delayed 24 months• Collected blood and coronal sulcus swabs every 6 months
    • 4. Coronal sulcusCircumcised Uncircumcised
    • 5. Outcomes• Nearly 60% reduction in HIV seroconversion in circumcised men over the course of 24 months. – Reduced rates of HPV in men – Reduced rates of Herpes in men – Reduced rates of Trichomonas vaginalis & bacterial vaginosis in female partners
    • 6. Models reduced seroconversion• Removal of the foreskin = decreased mucosal surface area• Changes in microbiome = decreased mucosal inflammation• Keratinization of the inner foreskin = thicker dermal layer protecting immune cells
    • 7. Microbiome Study Design• 77 men (control) and 79 men (intervention) from the Rakai Study – 312 Swab samples collected from the coronal sulcus • Baseline • 1 year• Bacterial quantification – 16S qPCR• Bacterial community characterization – 16S pyrosequencing
    • 8. Bacterial load
    • 9. -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 p = 0.048ControlIntervention 77 76 75 74 73 72 71 70 69 68 67 66 65 64 63 62 61 60 59 58 57 56 55 54 53 52 51 50 49 48 47 46 45 44 43 42 41 40 39 38 Control 37 36 35 34 33 32 31 30 29 28 27 26 25 24 23 22 21 20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 156 155 154 153 152 151 150 149 148 147 146 145 144 143 142 141 140 139 138 137 136 135 134 133 132 131 130 129 128 127 126 125 124 123 122 121 120 119 118 117 116 115 114 113 112 111 110 109 108 Intervention 107 106 105 104 103 102 101 100 99 98 97 96 95 94 93 92 91 90 89 88 87 86 85 84 83 82 81 80 79 78 -5 0 5 Log Response Ratio (16S rRNA gene copy)
    • 10. Community Analysis
    • 11. Our approach: who then what• Use 16S pyrosequencing to define the community composition• Characterize changes in abundance• Use indicator species analysis to identify key players• Evaluate their role in the community and relationship to the host
    • 12. 454 sequencing of 16S amplicons V6 V3 Phylogenetic Information V4 V5 0 200 400 600 800 1000 1200 1400 1600 Position in 16S rRNA gene
    • 13. Analysis chain
    • 14. Control Baseline Control Year 1 Campylobacteraceae Peptostreptococcaceae Streptococcaceae Prevotellaceae Actinomycetaceae Enterobacteriaceae Campylobacteraceae Peptostreptococcaceae Prevotellaceae Clostridiales.Family.XIb Streptococcaceae Actinomycetaceae Staphylococcaceae Enterobacteriaceae Clostridiales.Family.XIb Veillonellaceae Staphylococcaceae Veillonellaceae Bifidobacteriaceae Bifidobacteriaceae Corynebacteriaceae Corynebacteriaceae Porphyromonadaceae Porphyromonadaceae Lactobacillaceae Lactobacillaceae Clostridiales.Family.XIa Unclassified.Clostridiales Clostridiales.Family.XIa Unclassified.Clostridiales Intervention Baseline Intervention Year 1 Campylobacteraceae Peptostreptococcaceae Streptococcaceae Actinomycetaceae Enterobacteriaceae Prevotellaceae Clostridiales.Family.XIb Campylobacteraceae Peptostreptococcaceae Streptococcaceae Prevotellaceae Staphylococcaceae Actinomycetaceae Enterobacteriaceae Veillonellaceae Clostridiales.Family.XIb Staphylococcaceae Bifidobacteriaceae Veillonellaceae Bifidobacteriaceae CorynebacteriaceaePorphyromonadaceae Corynebacteriaceae Porphyromonadaceae Lactobacillaceae Unclassified.Clostridiales Clostridiales.Family.XIa Lactobacillaceae Clostridiales.Family.XIa Unclassified.Clostridiales
    • 15. Control BL Control Y1 0.6 0.4 0.2nMDS axis 2 0.0 -0.2 -0.4 -0.6 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 nMDS axis 1
    • 16. Intervention BL 0.6 Intervention Y1 (Post-Circ) 0.4 0.2nMDS axis 2 0.0 -0.2 -0.4 -0.6 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 nMDS axis 1
    • 17. nMDS plot of Baseline (BL) and Year 1 (Y1 ) Family-level Log-transformed Absolute Abundance Microbiota Control BL Control Y1 0.6 0.4 0.2nMDS axis 2 0.0 -0.2 -0.4 -0.6 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 Intervention BL 0.6 Intervention Y1 (Post-Circ) 0.4 0.2nMDS axis 2 0.0 -0.2 -0.4 -0.6 -0.6 -0.4 -0.2 0.0 0.2 0.4 0.6 nMDS axis 1
    • 18. Activated Langerhans cells present intact HIV to TCells Naïve Langerhans cells engulf and destroy HIV
    • 19. Future Directions• Inflammatory markers• Langerhans cells recruitment and activation in foreskins• Cell culture models of Langerhans activation HIV MC-associated genital bacterial changes Exciting, with low Exciting, with Exciting, with potential impact potential impact high impact
    • 20. Acknowledgements• TGen/NAU • Hopkins/Rakai – Cindy Liu – Ron Gray – Bruce Hungate – Maria Wawer – Maliha Aziz – Godfrey Kigozi – Richard Lester – David Serwadda – Tania Contente-Cuomo – Aaron Tobian – Paul Keim • Umaryland – Jacques Ravel Makerere University School of Public Health