葡萄糖增生療法對間質性膀胱炎患者尿液微生物組之影響

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姓名

陳良坤(Liang-Kun Chen) 查詢紙本館藏

畢業系所

生醫科學與工程學系

論文名稱

葡萄糖增生療法對間質性膀胱炎患者尿液微生物組之影響
(The Impact of Dextrose Prolotherapy on Urinary Microbiome in Interstitial Cystitis/Bladder Pain Syndrome)

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摘要(中)

間質性膀胱炎（IC/BPS）是一種以排尿功能紊亂和盆腔疼痛為特徵的慢性疾病，影響著全球數百萬人。此疾病主要病因尚不清楚，且症狀的複雜性導致診斷的不確定性，進而導致治療效果不佳。2021年研究發現葡萄糖增生療法對患者是安全的，並能增強對組織重塑的刺激，因此，期望透過16S片段定序研究尿液微生物組的變化以探討此療法的潛在治療機制。從對照組的健康參與者以及間質性膀胱炎患者接受葡萄糖增生療法前後，採集排出的中段尿液樣本，通過對尿液樣本進行 16S rRNA 基因測序，檢測尿液微生物組。在健康對照組和間質性膀胱炎患者之間觀察到尿液微生物組多樣性有顯著差異。間質性膀胱炎患者中變形菌門、厚壁菌門及擬桿菌門較豐富。重要的是，葡萄糖增殖療法導致有害細菌（Subgroup_22、Chryseolinea 和 Ureaplasma）減少，同時豐富了有益菌種，如Luteolibacter、Lactococcus,和 L. lactis，與臨床症狀的改善有關。葡萄糖增殖療法不僅可以減少間質性膀胱炎患者中有害細菌的存在，還可以促進有益微生物的生長。這些發現表明，尿液微生物組的調節可能是其治療成功的關鍵因素。

摘要(英)

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by disruptions in urinary function and the presence of pelvic pain that affects millions of people worldwide. The major etiology of IC/BPS remains unclear, compounded by the complexity of symptoms leading to diagnostic uncertainties and consequently, suboptimal treatment outcomes. The 2021 study demonstrated that dextrose prolotherapy was safe for patients with IC/BPS and enhanced stimulation of tissue remodeling. Thus, further exploration of the potential therapeutic mechanisms of dextrose prolotherapy is anticipated. Through 16S rRNA gene sequencing, this study aims to investigate the characteristics of the urinary microbiome in patients before and after receiving dextrose prolotherapy, seeking insights into its potential therapeutic mechanisms. Voided midstream urine samples were obtained from healthy participants and patients with IC/BPS before and after dextrose prolotherapy. Significant differences in urinary microbiome diversity were observed between healthy controls and IC/BPS patients. Proteobacteria, Firmicutes, and Bacteroidota were more abundant in IC/BPS patients. Importantly, dextrose prolotherapy led to a decrease in harmful bacteria (Subgroup_22, and Chryseolinea, and Ureaplasma) while enriching beneficial species such as Luteolibacter, Lactococcus, and L. lactis, correlating with improved clinical symptoms. Dextrose prolotherapy not only reduces the presence of harmful bacteria but also fosters the growth of beneficial microbes in IC/BPS patients. These findings suggest that the modulation of the urinary microbiome may be a key factor in its therapeutic success.

關鍵字(中)

★ 間質性膀胱炎
★ 膀胱疼痛綜合症
★ 16S測序
★ 葡萄糖增生療法
★ 微生物組
★ 尿液微生物組

關鍵字(英)

★ interstitial cystitis
★ bladder pain syndrome
★ 16S sequencing
★ dextrose prolotherapy
★ microbiome
★ urinary microbiome

論文目次

摘要 i
ABSTRACT ii
誌謝 iii
目錄 iv
圖目錄 v
表目錄 vi
一、緒論 1
1-1 間質性膀胱炎之症狀及患病率 1
1-2 間質性膀胱炎之病因、病理生理學和診斷 2
1-3 間質性膀胱炎治療方法 3
1-4 研究動機及目的 3
二、研究材料與方法 6
2-1 間質性膀胱炎患者與健康對照組 6
2-2 樣本採集與保存 6
2-3 尿液DNA萃取與16S rRNA基因擴增 7
2-4 16S rRNA基因擴增產物測序 8
2-5 生物資訊學和統計分析 8
三、結果 10
3-1 參與者的臨床特徵 10
3-2 健康對照組和間質性膀胱炎患者的尿液微生物多樣性 10
3-3 健康對照組和間質性膀胱炎患者的尿液微生組 11
3-4 與間質性膀胱炎致病相關菌屬 12
3-5 尿液微生態與間質性膀胱炎患者臨床指標之間的相關性 13
3-6 與致病相關及葡萄糖增生療法相關的重要微生物功能 13
四、討論 29
五、結論 33
參考文獻 34
附錄 44

參考文獻

1. Cox, A., Management of interstitial cystitis/bladder pain syndrome. Can Urol Assoc J, 2018. 12(6 Suppl 3): p. S157-s160.
2. Hanno, P., et al., International Consultation on IC - Rome, September 2004/Forging an International Consensus: progress in painful bladder syndrome/interstitial cystitis. Report and abstracts. Int Urogynecol J Pelvic Floor Dysfunct, 2005. 16 Suppl 1: p. S2-s34.
3. Hanno, P.M., et al., Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol, 2015. 193(5): p. 1545-53.
4. Patnaik, S.S., et al., Etiology, pathophysiology and biomarkers of interstitial cystitis/painful bladder syndrome. Archives of gynecology and obstetrics, 2017. 295: p. 1341-1359.
5. Clemens, J.Q., et al., Diagnosis and Treatment of Interstitial Cystitis/Bladder Pain Syndrome. J Urol, 2022. 208(1): p. 34-42.
6. Chancellor, M.B. and N. Yoshimura, Treatment of interstitial cystitis. Urology, 2004. 63(3): p. 85-92.
7. Nickel, J.C., Managing interstitial cystitis/bladder pain syndrome in female patients: Clinical recipes for success. Can Urol Assoc J, 2022. 16(12): p. 393-398.
8. Lee, M.H., K.M. Chang, and W.C. Tsai, Morbidity rate and medical utilization in interstitial cystitis/painful bladder syndrome. Int Urogynecol J, 2018. 29(7): p. 1045-1050.
9. Berry, S.H., et al., Prevalence of symptoms of bladder pain syndrome/interstitial cystitis among adult females in the United States. J Urol, 2011. 186(2): p. 540-4.
10. Masterson, J.M., P.R. Castaneda, and J. Kim, Pathophysiology and Clinical Biomarkers in Interstitial Cystitis. Urol Clin North Am, 2023. 50(1): p. 39-52.
11. Abdal Dayem, A., et al., Application of Adult and Pluripotent Stem Cells in Interstitial Cystitis/Bladder Pain Syndrome Therapy: Methods and Perspectives. Journal of Clinical Medicine, 2020. 9(3): p. 766.
12. Akiyama, Y., Biomarkers in Interstitial Cystitis/Bladder Pain Syndrome with and without Hunner Lesion: A Review and Future Perspectives. Diagnostics (Basel), 2021. 11(12).
13. Kuret, T., et al., A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome. Biomedicines, 2021. 9(8).
14. Meng, E., Y.C. Hsu, and Y.C. Chuang, Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial cystitis (IC). Low Urin Tract Symptoms, 2018. 10(1): p. 3-11.
15. Riedl, C.R., et al., Hyaluronan treatment of interstitial cystitis/painful bladder syndrome. Int Urogynecol J Pelvic Floor Dysfunct, 2008. 19(5): p. 717-21.
16. Manning, J., et al., A multicentre, prospective, randomised, double-blind study to measure the treatment effectiveness of abobotulinum A (AboBTXA) among women with refractory interstitial cystitis/bladder pain syndrome. Int Urogynecol J, 2014. 25(5): p. 593-9.
17. Chen, C.-L., et al., A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome. Frontiers in pharmacology, 2021. 12: p. 755615-755615.
18. Parsons, C.L., et al., Alkalinized lidocaine and heparin provide immediate relief of pain and urgency in patients with interstitial cystitis. J Sex Med, 2012. 9(1): p. 207-12.
19. Nasta, L., The Prevalence of Bladder Pain Syndrome/Interstitial Cystitis in Italy: The importance of a National Registry, in Bladder Pain Syndrome – An Evolution, P.M. Hanno, et al., Editors. 2018, Springer International Publishing: Cham. p. 27-32.
20. Nickel, J.C., et al., The Interstitial Cystitis/Bladder Pain Syndrome Clinical Picture: A Perspective from Patient Life Experience. Urology Practice, 2018. 5(4): p. 286-292.
21. Tripp, D.A., et al., Depression and catastrophizing predict suicidal ideation in tertiary care patients with interstitial cystitis/bladder pain syndrome. Can Urol Assoc J, 2016. 10(11-12): p. 383-388.
22. Sutherland, S., et al., Compensatory coping and depression in women with interstitial cystitis/bladder pain syndrome. Neurourology and Urodynamics, 2023. 42(1): p. 322-329.
23. Crawford, A., et al., Depression and helplessness impact interstitial cystitis/bladder pain syndrome pain over time. Canadian Urological Association Journal, 2019. 13(10): p. 328.
24. Alexander, K.L., S.R. Targan, and C.O. Elson, 3rd, Microbiota activation and regulation of innate and adaptive immunity. Immunol Rev, 2014. 260(1): p. 206-20.
25. Hou, K., et al., Microbiota in health and diseases. Signal transduction and targeted therapy, 2022. 7(1): p. 135.
26. Keay, S., et al., A prospective study of microorganisms in urine and bladder biopsies from interstitial cystitis patients and controls. Urology, 1995. 45(2): p. 223-229.
27. Domingue, G.J., et al., Dormant microbes in interstitial cystitis. The Journal of urology, 1995. 153(4): p. 1321-1326.
28. Wolfe, A.J., et al., Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol, 2012. 50(4): p. 1376-83.
29. Hilt, E.E., et al., Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol, 2014. 52(3): p. 871-6.
30. Whiteside, S.A., et al., The microbiome of the urinary tract--a role beyond infection. Nat Rev Urol, 2015. 12(2): p. 81-90.
31. Aragon, I.M., et al., The Urinary Tract Microbiome in Health and Disease. Eur Urol Focus, 2018. 4(1): p. 128-138.
32. Xu, H., et al., Combined Signature of the Urinary Microbiome and Metabolome in Patients With Interstitial Cystitis. Front Cell Infect Microbiol, 2021. 11: p. 711746.
33. Zheng, Z., et al., Integrated microbiome and metabolome analysis reveals novel urinary microenvironmental signatures in interstitial cystitis/bladder pain syndrome patients. J Transl Med, 2023. 21(1): p. 266.
34. Choi, H.W., K.W. Lee, and Y.H. Kim, Microbiome in urological diseases: Axis crosstalk and bladder disorders. Investig Clin Urol, 2023. 64(2): p. 126-139.
35. Saha, S.K., et al., Bioinformatics Approach for Identifying Novel Biomarkers and Their Signaling Pathways Involved in Interstitial Cystitis/Bladder Pain Syndrome with Hunner Lesion. J Clin Med, 2020. 9(6).
36. Bolyen, E., et al., Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol, 2019. 37(8): p. 852-857.
37. Quast, C., et al., The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic acids research, 2013. 41(Database issue): p. D590-D596.
38. Caporaso, J.G., et al., QIIME allows analysis of high-throughput community sequencing data. Nature methods, 2010. 7(5): p. 335-336.
39. Oksanen, J., et al., Vegan: community ecology package http://CRAN. R-project. org/package= vegan, 2013.
40. Warnes, G.R., et al., gplots: Various R programming tools for plotting data. R package version, 2009. 2(4): p. 1.
41. Parks, D.H., et al., STAMP: statistical analysis of taxonomic and functional profiles. Bioinformatics, 2014. 30(21): p. 3123-3124.
42. Jonsson, V., et al., Statistical evaluation of methods for identification of differentially abundant genes in comparative metagenomics. BMC genomics, 2016. 17(1): p. 1-14.
43. Love, M.I., W. Huber, and S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome biology, 2014. 15(12): p. 1-21.
44. Langille, M.G., et al., Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nature biotechnology, 2013. 31(9): p. 814-821.
45. Wolfe, A.J., et al., Detection of Bacteria in Bladder Mucosa of Adult Females. J Urol, 2023: p. 101097ju0000000000003189.
46. Bresler, L., et al., Female lower urinary tract microbiota do not associate with IC/PBS symptoms: a case-controlled study. International Urogynecology Journal, 2019. 30(11): p. 1835-1842.
47. Meriwether, K.V., et al., The Vaginal and Urinary Microbiomes in Premenopausal Women With Interstitial Cystitis/Bladder Pain Syndrome as Compared to Unaffected Controls: A Pilot Cross-Sectional Study. Front Cell Infect Microbiol, 2019. 9: p. 92.
48. Siddiqui, H., et al., Alterations of microbiota in urine from women with interstitial cystitis. BMC Microbiol, 2012. 12: p. 205.
49. Chen, Y.B., et al., The Urethral Microbiota: A Missing Link in the Female Urinary Microbiota. J Urol, 2020. 204(2): p. 303-309.
50. Pearce, M.M., et al., The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio, 2014. 5(4): p. e01283-14.
51. Heritz, D.M., et al., Detection of eubacteria in interstitial cystitis by 16S rDNA amplification. J Urol, 1997. 158(6): p. 2291-5.
52. Au, C.W., et al., Exit site infection and peritonitis due to Serratia species in patients receiving peritoneal dialysis: epidemiology and clinical outcomes. Nephrology, 2021. 26(3): p. 255-261.
53. Bhattarai, D., et al., Infection Due to Serratia sp. in Chronic Granulomatous Disease—Is the Incidence Low in Tropical Countries? Journal of Clinical Immunology, 2021. 41(2): p. 486-490.
54. Hmida, S.B., et al., Pseudomonas Luteola Infection: First Case Report of Urinary Tract Infection and Review of Literature. Electronic Journal of General Medicine, 2021. 18(5).
55. Lamas Ferreiro, J.L., et al., Pseudomonas aeruginosa urinary tract infections in hospitalized patients: Mortality and prognostic factors. PloS one, 2017. 12(5): p. e0178178.
56. Villalba, N., et al., Lung infection by Pseudomonas aeruginosa induces neuroinflammation and blood–brain barrier dysfunction in mice. Journal of Neuroinflammation, 2023. 20(1): p. 127.
57. Zafar, H. and M.H. Saier Jr, Gut Bacteroides species in health and disease. Gut Microbes, 2021. 13(1): p. 1848158.
58. Goldstein, E.J., et al., Desulfovibrio desulfuricans bacteremia and review of human Desulfovibrio infections. J Clin Microbiol, 2003. 41(6): p. 2752-4.
59. Murros, K.E., et al., Desulfovibrio bacteria are associated with Parkinson’s disease. Frontiers in Cellular and Infection Microbiology, 2021. 11: p. 652617.
60. de Blackburn, C.W. and P.J. McClure, Pathogenic Bacillus species, in Foodborne Pathogens (second edition). 2009, Woodhead Publishing. p. 844-888.
61. Turnbull, P.C.B., Bacillus, in Medical Microbiology (4th edition). 1996, Galveston (TX): University of Texas Medical Branch at Galveston. Chapter 15.
62. Wan, Z., et al., Lactobacillus johnsonii YH1136 plays a protective role against endogenous pathogenic bacteria induced intestinal dysfunction by reconstructing gut microbiota in mice exposed at high altitude. Frontiers in Immunology, 2022. 13: p. 1007737.
63. Gervasi, T., et al., Application of Lactobacillus johnsonii expressing phage endolysin for control of Clostridium perfringens. Letters in Applied Microbiology, 2014. 59(4): p. 355-361.
64. Davoren, M.J., et al., A novel probiotic, Lactobacillus johnsonii 456, resists acid and can persist in the human gut beyond the initial ingestion period. Gut Microbes, 2019. 10(4): p. 458-480.
65. Huang, C.-H., et al., The probiotic activity of Lactobacillus murinus against food allergy. Journal of Functional Foods, 2016. 25: p. 231-241.
66. Abernethy, M.G. and A. Tsuei, The bladder microbiome and interstitial cystitis: is there a connection? Current Opinion in Obstetrics and Gynecology, 2021. 33(6).
67. Bschleipfer, T. and I. Karl, Bladder Microbiome in the Context of Urological Disorders—Is There a Biomarker Potential for Interstitial Cystitis? Diagnostics, 2022. 12(2): p. 281.
68. Nickel, J.C., 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): p. 415.
69. Kokkayil, P. and B. Dhawan, Ureaplasma: Current perspectives. Indian Journal of Medical Microbiology, 2015. 33(2): p. 205-214.
70. Liu, W., et al., Ureaplasma infections: update on epidemiology, antimicrobial resistance, and pathogenesis. Critical Reviews in Microbiology: p. 1-31.
71. Tantengco, O.A.G., et al., Inflammatory response elicited by Ureaplasma parvum colonization in human cervical epithelial, stromal, and immune cells. Reproduction, 2022. 163(1): p. 1-10.
72. Silwedel, C., et al., More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells. Journal of Neuroinflammation, 2019. 16(1): p. 38.
73. Akazawa, Y., et al., Inhibition of arginase ameliorates experimental ulcerative colitis in mice. Free Radic Res, 2013. 47(3): p. 137-45.
74. Li, J.-Y., et al., Arginine metabolism regulates the pathogenesis of inflammatory bowel disease. Nutrition Reviews, 2022. 81(5): p. 578-586.
75. Baier, J., et al., Arginase impedes the resolution of colitis by altering the microbiome and metabolome. J Clin Invest, 2020. 130(11): p. 5703-5720.
76. Luerce, T.D., et al., Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically induced colitis. Gut Pathog, 2014. 6: p. 33.
77. Ramalho, J.B., et al., In Vitro Probiotic and Antioxidant Potential of Lactococcus lactis subsp. cremoris LL95 and Its Effect in Mice Behaviour. Nutrients, 2019. 11(4): p. 901.
78. Ma, J., et al., 5-HT attenuates chronic stress-induced cognitive impairment in mice through intestinal flora disruption. Journal of Neuroinflammation, 2023. 20(1): p. 23.

指導教授

許藝瓊(Yi-Chiung Hsu)

審核日期

2025-1-13

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