A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network
Abstract
1. Introduction
2. Experimental Section
2.1. Participants and Specimens
2.2. Specimen Handling
2.3. DNA Extraction and Ibis Eubacterial and Fungal Domain Assays on the PLEX-ID
2.4. Statistical Analysis
3. Results
3.1. Demographic Data
3.2. Clinical Data
3.3. Species Data
3.4. Genus Data
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Appendix A. NIH/NIDDK MAPP Network
Appendix B. Inclusion and Exclusion Criteria for MAPP 1. Adapted from [24]
Appendix B.1. Inclusion Criteria
Appendix B.2. Exclusion Criteria
Appendix B.3. Eligibility Criteria for Controls
Appendix C. Details of Methodology in Regard to PLEX-ID Analysis
References
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Parameter | Category | *IC/BPS | Controls | Total | p |
---|---|---|---|---|---|
Number of Participants | n (%) | 181 | 182 | 363 | |
Clinical Site | Northwestern U | 17 (9.4%) | 22 (12.1%) | 39 (10.7%) | 0.906 |
UCLA | 25 (13.8%) | 24 (13.2%) | 49 (13.5%) | ||
U of Iowa | 36 (19.9%) | 29 (15.9%) | 65 (17.9%) | ||
U of Michigan | 33 (18.2%) | 33 (18.1%) | 66 (18.2%) | ||
U of Washington | 23 (12.7%) | 29 (15.9%) | 52 (14.3%) | ||
Wash U St. Louis | 39 (21.5%) | 37 (20.3%) | 76 (20.9%) | ||
Stanford U | 8 (4.4%) | 8 (4.4%) | 16 (4.4%) | ||
Age Group | <35 years | 76 (42.0%) | 81 (44.5%) | 157 (43.3%) | 0.869 |
35–50 years | 50 (27.6%) | 50 (27.5%) | 100 (27.5%) | ||
50+ years | 55 (30.4%) | 51 (28.0%) | 106 (29.2%) | ||
Race | White | 165 (91.2%) | 137 (75.3%) | 302 (83.2%) | <0.001 |
Black | 5 (2.8%) | 25 (13.7%) | 30 (8.3%) | ||
Asian | 2 (1.1%) | 10 (5.5%) | 12 (3.3%) | ||
Multi Race | 3 (1.7%) | 5 (2.7%) | 8 (2.2%) | ||
Other | 5 (2.8%) | 4 (2.2%) | 9 (2.5%) | ||
Unknown | 1 (0.6%) | 1 (0.5%) | 2 (0.6%) | ||
Ethnicity | Hispanic | 11 (6.1%) | 11 (6.0%) | 22 (6.1%) | 1.000 |
Non-Hispanic | 170 (93.9%) | 171 (94.0%) | 341 (93.9%) |
Parameter | Category | IC/BPS | Controls | Total | p |
---|---|---|---|---|---|
Number of Participants | n (%) | 181 | 182 | 363 | |
Self-reported IC diagnosis | No | 24 (13.3%) | 169 (92.9%) | 193 (53.2%) | <0.001 |
Yes | 157 (86.7%) | 2 (1.1%) | 159 (43.8%) | ||
Missing | 11 (6.0%) | 11 (3.0%) | |||
Meet MAPP IC/BPS Criteria | Yes | 181 (100.0%) | 181 (49.9%) | ||
Missing | 182 (100.0%) | 182 (50.1%) | |||
IC diagnosis from Rice form | No | 64 (35.4%) | 172 (94.5%) | 236 (65.0%) | <0.001 |
Yes | 117 (64.6%) | 10 (5.5%) | 127 (35.0%) | ||
Associated Chronic Pain Syndrome | None | 105 (58.0%) | 110 (60.4%) | 215 (59.2%) | 0.670 |
Any Syndrome | 76 (42.0%) | 72 (39.6%) | 148 (40.8%) | ||
Interstitial Cystitis Symptom Index (ICSI) | 10.9 (4.4) | 3.0 (3.2) | 7.0 (5.5) | <0.001 | |
Genitourinary Pain Index (GUPI) | 26.6 (8.7) | 4.7 (7.4) | 15.7 (13.6) | <0.001 | |
Meds for urologic or pelvic pain symptoms | No | 37 (20.4%) | 176 (96.7%) | 213 (58.7%) | <0.001 |
Yes | 144 (79.6%) | 6 (3.3%) | 150 (41.3%) | ||
Pain medication class | None | 36 (19.9%) | 121 (66.5%) | 157 (43.3%) | <0.001 |
Peripheral | 42 (23.2%) | 24 (13.2%) | 66 (18.2%) | ||
Central | 81 (44.8%) | 28 (15.4%) | 109 (30.0%) | ||
Opioid | 22 (12.2%) | 9 (4.9%) | 31 (8.5%) |
Species unique to IC/BPS | Species unique to Controls | Species found in both: |
---|---|---|
1. Acinetobacter grimontii | 1. Bordetella parapertussis | 1. Bacteroides ureolyticus |
2. Akkermansia muciniphila | 2. Burkholderia sp. | 2. Bifidobacterium inopinatum |
3. Bacillus sp. | 3. Clostridium sp. | 3. Bifidobacterium longum |
4. Bifidobacterium bifidum | 4. Enterococcus faecium | 4. Bifidobacterium subtile |
5. Bifidobacterium infantis | 5. Haemophilus influenzae | 5. Bordetella bronchiseptica |
6. Borrelia turicatae | 6. Klebsiella oxytoca | 6. Burkholderia cenocepacia |
7. Candida dubliniensis | 7. Klebsiella pneumoniae | 7. Candida albicans |
8. Clostridium perfringens | 8. Lactobacillus collinoides | 8. Candida glabrata |
9. Escherichia coli | 9. Ochrobactrum anthropi | 9. Corynebacterium diphtheriae |
10. Helicobacter hepaticus | 10. Pasteurella multocida | 10. Corynebacterium jeikeium |
11. Lactobacillus casei | 11. Pediococcus pentosaceus | 11. Corynebacterium pseudodiphtheriticum |
12. Lactobacillus helveticus | 12. Pseudomonas stutzeri | |
13. Lactobacillus reuteri | 13. Serratia marcescens | |
14. Lactococcus lactis | 14. Streptococcus mutans | |
15. Proteus mirabilis | 15. Streptococcus sanguinis | |
16. Pseudomonas aeruginosa | 16. Treponema denticola | |
17. Salmonella enterica | 17. Ureaplasma urealyticum | |
18. Staphylococcus intermedius | 18. Francisella philomiragia | |
19. Streptococcus dysgalactiae | 19. Corynebacterium striatum | |
20. Streptococcus porcinus | 20. Microbacterium sp. | |
21. Streptococcus pyogenes | ||
22. Bacteroides vulgatus | ||
23. Bifidobacterium pseudocatenulatum | ||
24. Francisella tularensis | ||
25. Mycoplasma hyorhinis | ||
26. Paracoccus denitrificans | ||
27. Staphylococcus sp. | ||
28. Micrococcus lylae | ||
29. Tetragenococcus halophilus |
Taxonomic Level | Index | Controls | UCPPS | p1 | ||
---|---|---|---|---|---|---|
n | Mean (SD) | n | Mean (SD) | |||
Species | Chao1 | 182 | 2.3 (1.3) | 181 | 2.5 (1.5) | 0.18 |
Shannon | 182 | 0.2 (0.3) | 181 | 0.3 (0.3) | 0.15 | |
Genus | Chao1 | 182 | 1.9 (1.1) | 181 | 2 (1.1) | 0.41 |
Shannon | 182 | 0.2 (0.3) | 181 | 0.2 (0.3) | 0.38 |
Controls | UCPPS | Associate: Prevalence | Association: Relative Abundance | |||||
---|---|---|---|---|---|---|---|---|
taxa | Prevalence | Mean (SD) Relative Abundance | Prevalence | Mean (SD) Relative Abundance | OR (95% CI) | p1 | Mean Difference | p2 |
Staphylococcus hominis | 20/182 (11%) | 0.01 (0.055) | 29/181 (16%) | 0.014 (0.091) | 1.55 (0.84,2.85) | 0.163 | 0.004 | 0.216 |
Staphylococcus lugdunensis | 6/182 (3.3%) | 0.012 (0.106) | 6/181 (3.3%) | 0.002 (0.016) | 1.01 (0.32,3.18) | 0.992 | −0.011 | 0.996 |
Staphylococcus warneri | 10/182 (5.5%) | 0.011 (0.091) | 4/181 (2.2%) | 0.003 (0.043) | 0.39 (0.12,1.26) | 0.116 | −0.008 | 0.098 |
Streptococcus agalactiae | 11/182 (6%) | 0.009 (0.068) | 11/181 (6.1%) | 0.008 (0.078) | 1.01 (0.42,2.38) | 0.989 | −0.001 | 0.972 |
Bifidobacterium subtile | 26/182 (14.3%) | 0.128 (0.322) | 26/181 (14.4%) | 0.106 (0.282) | 1.01 (0.56,1.81) | 0.982 | −0.022 | 0.872 |
Burkholderia cenocepacia | 12/182 (6.6%) | 0.018 (0.128) | 8/181 (4.4%) | 0.019 (0.128) | 0.66 (0.26,1.64) | 0.367 | 0.001 | 0.389 |
Finegoldia magna | 10/182 (5.5%) | 0.018 (0.113) | 12/181 (6.6%) | 0.004 (0.029) | 1.22 (0.51,2.9) | 0.651 | −0.014 | 0.703 |
Lactobacillus acidophilus | 21/182 (11.5%) | 0.062 (0.223) | 20/181 (11%) | 0.06 (0.22) | 0.95 (0.5,1.82) | 0.883 | −0.002 | 0.878 |
Lactobacillus crispatus | 54/182 (29.7%) | 0.277 (0.434) | 51/181 (28.2%) | 0.258 (0.419) | 0.93 (0.59,1.46) | 0.753 | −0.019 | 0.415 |
Lactobacillus gasseri | 5/182 (2.7%) | 0.015 (0.11) | 12/181 (6.6%) | 0.024 (0.122) | 2.51 (0.87,7.29) | 0.090 | 0.009 | 0.084 |
Lactobacillus johnsonii | 45/182 (24.7%) | 0.027 (0.127) | 51/181 (28.2%) | 0.038 (0.146) | 1.19 (0.75,1.91) | 0.456 | 0.012 | 0.329 |
Lactobacillus sp. | 11/182 (6%) | 0.059 (0.233) | 11/181 (6.1%) | 0.055 (0.218) | 1.01 (0.42,2.38) | 0.989 | −0.004 | 0.96 |
Listeria innocua/monocytogenes | 8/182 (4.4%) | 0.013 (0.098) | 5/181 (2.8%) | 0.001 (0.016) | 0.62 (0.2,1.93) | 0.407 | −0.012 | 0.39 |
Propionibacterium acnes | 10/182 (5.5%) | 0.036 (0.173) | 12/181 (6.6%) | 0.03 (0.145) | 1.22 (0.51,2.9) | 0.651 | −0.007 | 0.686 |
Staphylococcus aureus | 6/182 (3.3%) | 0.006 (0.051) | 4/181 (2.2%) | 0.001 (0.008) | 0.66 (0.18,2.39) | 0.560 | −0.005 | 0.524 |
Staphylococcus capitis/caprae | 8/182 (4.4%) | 0.009 (0.077) | 7/181 (3.9%) | 0.016 (0.108) | 0.88 (0.31,2.47) | 0.801 | 0.007 | 0.814 |
Staphylococcus epidermidis/haemolyticus | 57/182 (31.3%) | 0.05 (0.184) | 61/181 (33.7%) | 0.042 (0.171) | 1.11 (0.72,1.73) | 0.628 | −0.007 | 0.816 |
Staphylococcus haemolyticus | 10/182 (5.5%) | 0.004 (0.037) | 11/181 (6.1%) | 0.004 (0.031) | 1.11 (0.46,2.69) | 0.812 | 0.000 | 0.819 |
Controls | UCPPS | Associate: Prevalence | Association: Relative Abundance | |||||
---|---|---|---|---|---|---|---|---|
Taxa | Prevalence | Mean (SD) Relative Abundance | Prevalence | Mean (SD) Relative Abundance | OR (95% CI) | p1 | Mean Difference | p2 |
Bifidobacterium | 28/182 (15.4%) | 0.138 (0.333) | 35/181 (19.3%) | 0.148 (0.327) | 1.32 (0.76,2.28) | 0.321 | 0.009 | 0.461 |
Burkholderia | 13/182 (7.1%) | 0.023 (0.147) | 8/181 (4.4%) | 0.019 (0.128) | 0.6 (0.24,1.49) | 0.271 | −0.004 | 0.283 |
Candida | 5/182 (2.7%) | 0 (0.004) | 11/181 (6.1%) | 0.009 (0.078) | 2.29 (0.78,6.73) | 0.132 | 0.008 | 0.119 |
Corynebacterium | 23/182 (12.6%) | 0.08 (0.248) | 6/181 (3.3%) | 0.012 (0.085) | 0.24 (0.09,0.6) | 0.002* | −0.068 | 0.001 * |
Finegoldia | 10/182 (5.5%) | 0.018 (0.113) | 12/181 (6.6%) | 0.004 (0.029) | 1.22 (0.51,2.9) | 0.651 | −0.014 | 0.703 |
Lactobacillus | 104/182 (57.1%) | 0.457 (0.473) | 109/181 (60.2%) | 0.461 (0.461) | 1.14 (0.75,1.72) | 0.552 | 0.004 | 0.822 |
Listeria | 8/182 (4.4%) | 0.013 (0.098) | 5/181 (2.8%) | 0.001 (0.016) | 0.62 (0.2,1.93) | 0.407 | −0.012 | 0.39 |
Propionibacterium | 10/182 (5.5%) | 0.036 (0.173) | 12/181 (6.6%) | 0.03 (0.145) | 1.22 (0.51,2.9) | 0.651 | −0.007 | 0.686 |
Staphylococcus | 101/182 (55.5%) | 0.107 (0.258) | 99/181 (54.7%) | 0.103 (0.263) | 0.97 (0.64,1.46) | 0.879 | −0.004 | 0.511 |
Streptococcus | 17/182 (9.3%) | 0.018 (0.099) | 26/181 (14.4%) | 0.035 (0.156) | 1.63 (0.85,3.12) | 0.141 | 0.017 | 0.141 |
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Nickel, J.C.; Stephens-Shields, A.J.; Landis, J.R.; Mullins, C.; van Bokhoven, A.; Lucia, M.S.; Henderson, J.P.; Sen, B.; Krol, J.E.; Ehrlich, G.D.; et al. A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network. J. Clin. Med. 2019, 8, 415. https://doi.org/10.3390/jcm8030415
Nickel JC, Stephens-Shields AJ, Landis JR, Mullins C, van Bokhoven A, Lucia MS, Henderson JP, Sen B, Krol JE, Ehrlich GD, et al. A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network. Journal of Clinical Medicine. 2019; 8(3):415. https://doi.org/10.3390/jcm8030415
Chicago/Turabian StyleNickel, J. Curtis, Alisa J. Stephens-Shields, J. Richard Landis, Chris Mullins, Adrie van Bokhoven, M. Scott Lucia, Jeffrey P. Henderson, Bhaswati Sen, Jaroslaw E. Krol, Garth D. Ehrlich, and et al. 2019. "A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network" Journal of Clinical Medicine 8, no. 3: 415. https://doi.org/10.3390/jcm8030415
APA StyleNickel, J. C., Stephens-Shields, A. J., Landis, J. R., Mullins, C., van Bokhoven, A., Lucia, M. S., Henderson, J. P., Sen, B., Krol, J. E., Ehrlich, G. D., & The MAPP Research Network. (2019). A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis/Bladder Pain Syndrome Participants in the MAPP Research Network. Journal of Clinical Medicine, 8(3), 415. https://doi.org/10.3390/jcm8030415