THE EFFECT OF MICROBIAL PROFILE ON RESPONSE TO NONSURGICAL TREATMENT OF LOCALIZED AGGRESSIVE PERIODONTITIS By ALEXANDER FETNER A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE UNIVERSITY OF FLORIDA 2017 © 2017 Alexander Fetner To my girlfriend, Jackie, for her support during this tedious process ACKNOWLEDGMENTS I would like to thank my family for all of their support over the years, without which, I would not be where I am today. I would like to thank my colleagues at the University of Florida. Finally, I would also like to thank my mentors at the University of Florida, both clinical and research faculty, who have had a profound impact on my education. 4 TABLE OF CONTENTS page ACKNOWLEDGMENTS .................................................................................................. 4 LIST OF TABLES ............................................................................................................ 7 LIST OF FIGURES .......................................................................................................... 9 LIST OF ABBREVIATIONS ........................................................................................... 10 ABSTRACT ................................................................................................................... 11 CHAPTER 1 INTRODUCTION .................................................................................................... 13 Periodontitis ............................................................................................................ 13 Host Susceptibility to Aggressive Periodontitis ....................................................... 16 Microbiological Response to Periodontal Therapy .................................................. 22 Clinical Response to Nonsurgical Periodontal Therapy .......................................... 25 2 MATERIALS AND METHODS ................................................................................ 29 Subject Demographics ............................................................................................ 29 Clinical Measurements............................................................................................ 29 Collection of Sub-gingival Biofilm ............................................................................ 30 DNA Isolation and Microarray Analysis ................................................................... 30 Treatment ............................................................................................................... 31 Statistical Analysis .................................................................................................. 33 3 RESULTS ............................................................................................................... 35 Subject Demographics ............................................................................................ 35 PD Response to Treatment .................................................................................... 35 Bacterial Species in which Higher Baseline Levels are Associated with PD Non- Response to Treatment ....................................................................................... 36 Associations between Bacterial Species and PD Response to Treatment ............. 36 CAL Response to Treatment .................................................................................. 38 Associations between Bacterial Species and CAL in Response to Treatment ........ 39 4 DISCUSSION ......................................................................................................... 85 Limitations of Study ................................................................................................ 94 Conclusions ............................................................................................................ 98 LIST OF REFERENCES ............................................................................................... 99 5 BIOGRAPHICAL SKETCH .......................................................................................... 109 6 LIST OF TABLES Table page 3-1 Study Demographics .......................................................................................... 45 3-2 Sensitivity analysis for PD response ................................................................... 46 3-3 Sensitivity analysis for PD response (aggregated) ............................................. 47 3-4 Bacterial species in which presence at baseline is associated with non- responding PD sites ........................................................................................... 48 3-5 Bacterial species in which presence at baseline is associated with responding PD sites .................................................................................................................... 49 3-6 Sensitivity analysis for PD response at 3 Months ............................................... 50 3-7 Bacterial species in which presence at 3-month recall is associated with non- responding PD site ............................................................................................. 51 3-8 Bacterial species in which presence at 3-month recall is associated with responding PD sites ........................................................................................... 52 3-9 Sensitivity analysis for PD response at 12 Months ............................................. 53 3-10 Bacterial species in which presence at 12-month recall is associated with non- responding PD sites ........................................................................................... 54 3-11 Bacterial species in which presence at 12-month recall is associated with responding PD sites ........................................................................................... 55 3-12 Sensitivity analysis for CAL response (stringent)................................................ 56 3-13 Sensitivity analysis for CAL response (stringent, aggregated) ........................... 57 3-14 Bacterial species in which presence at baseline is associated with non- responding CAL sites (stringent criteria) ............................................................. 58 3-15 Bacterial species in which presence at baseline is associated with responding CAL sites (stringent criteria) ............................................................................... 60 3-16 Sensitivity analysis for CAL response (non-stringent) ........................................ 61 3-17 Sensitivity analysis for CAL response (non-stringent, aggregated) .................... 62 3-18 Bacterial species in which presence at baseline is associated with non- responding CAL sites (non-stringent criteria) ..................................................... 63 7 3-19 Bacterial species in which presence at baseline is associated with responding CAL sites (non-stringent criteria) ........................................................................ 66 3-20 Sensitivity analysis for CAL response at 3 Months ............................................. 67 3-21 Bacterial species in which presence at 3-month recall is associated with non- responding CAL sites (stringent criteria) ............................................................. 68 3-22 Bacterial species in which presence at 3-month recall is associated with responding CAL sites (stringent criteria) ............................................................. 69 3-23 Sensitivity analysis for CAL response at 12 Months ........................................... 70 3-24 Bacterial species in which presence at 12-month recall is associated with non- responding CAL sites (stringent criteria) ............................................................. 71 3-25 Bacterial species in which presence at 12-month recall is associated with responding CAL sites (stringent criteria) ............................................................. 72 3-26 Distribution of CAL Change at 3 Months Versus BL ........................................... 74 3-27 Sensitivity analysis for CAL Change at 3 Months Versus BL .............................. 75 3-28 Bacterial species in which Presence at BL is Associated with CAL Gain < 2 mm (or CAL loss) at 3 Months ................................................................................... 76 3-29 Bacterial species in which Presence at BL is Associated with CAL Gain ≥ 2 mm at 3 Months ......................................................................................................... 76 8 LIST OF FIGURES Figure page 3-1 Mean PD of Diseased Sites ................................................................................ 77 3-2 PD Reduction versus BL PD............................................................................... 77 3-3 (PCA Analysis): PD responders vs. non-responders .......................................... 78 3-4 (PCA Analysis): PD responders vs. non-responders at 3 months ...................... 79 3-5 (PCA Analysis): PD responders vs. non-responders at 12 months .................... 80 3-6 Mean CAL of Diseased Sites .............................................................................. 81 3-7 (PCA Analysis): stringent CAL responders vs. non-responders ......................... 82 3-8 (PCA Analysis): non-stringent CAL responders vs. non-responders .................. 83 3-9 PCA Analysis:Non-stringent CAL Responders vs. Non-responders at 3 Months 84 9 LIST OF ABBREVIATIONS