{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:40:21Z","timestamp":1785404421259,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"crossref","award":["1211425N"],"award-info":[{"award-number":["1211425N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"crossref","award":["1801125N"],"award-info":[{"award-number":["1801125N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1211425N"],"award-info":[{"award-number":["1211425N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1801125N"],"award-info":[{"award-number":["1801125N"]}],"id":[{"id":"https:\/\/ror.org\/03qtxy027","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Chronic pain is increasingly conceptualized as a systemic condition characterized by central sensitization, autonomic dysregulation, and persistent neuroimmune and neuroendocrine alterations. These systemic changes have been linked to microbial dysbiosis, most prominently within the gut microbiome. In contrast, the relevance of the urinary microbiome outside primary urological disease remains poorly understood, particularly in non-urological chronic pain conditions. The objective of this study was to determine whether patients with chronic low back pain exhibit differences in urinary microbial diversity, community composition, or taxon-specific abundance compared with pain-free controls. Methods: In this age- and sex-matched case\u2013control study, midstream urine samples were collected from ten patients with chronic low back pain and ten pain-free controls and analyzed using 16S rRNA gene sequencing (V4 region). Sequence data were processed using nf-core\/ampliseq and DADA2. Alpha diversity, beta diversity, and differential abundance were assessed using depth-adjusted models, compositional and phylogenetically informed distance metrics, and ANCOM-BC2, with multiple sensitivity analyses to account for the low-biomass nature of urinary microbiome data. Results: After accounting for sequencing depth, no significant differences in alpha diversity were observed between patients and controls for any metric. Beta diversity analyses revealed no significant differences in overall community composition between groups across all distance measures, and dispersion was comparable between groups. Differential abundance analysis did not identify any bacterial taxa that differed significantly between patients and controls after correction for multiple testing. Conclusions: In this cohort, chronic low back pain was not associated with detectable alterations in the urinary microbiome. These findings suggest that, unlike the gut microbiome, urinary microbial communities may be relatively stable in the context of non-urological chronic pain, highlighting the importance of phenotype specificity and multidimensional approaches in microbiome-based pain research.<\/jats:p>","DOI":"10.3390\/jcm15134931","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:14:12Z","timestamp":1782375252000},"page":"4931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Not All Microbiomes Reflect Chronic Pain: Evidence from the Urinary Tract in a Case\u2013Control Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2271-9855","authenticated-orcid":false,"given":"Lisa","family":"Goudman","sequence":"first","affiliation":[{"name":"STIMULUS Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Neurosurgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"},{"name":"Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Research Foundation\u2014Flanders (FWO), 1090 Brussels, Belgium"},{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0577-5449","authenticated-orcid":false,"given":"Maarten","family":"Moens","sequence":"additional","affiliation":[{"name":"STIMULUS Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Neurosurgery, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"},{"name":"Center for Neurosciences (C4N), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Research Foundation\u2014Flanders (FWO), 1090 Brussels, Belgium"},{"name":"Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium"},{"name":"Department of Radiology, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: Implications for the diagnosis and treatment of pain","volume":"152","author":"Woolf","year":"2011","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2174\/1570159X20666221012112725","article-title":"Central Sensitization and Pain: Pathophysiologic and Clinical Insights","volume":"22","author":"Curatolo","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1152\/physrev.00040.2019","article-title":"Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain","volume":"101","author":"Kuner","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/S0301-0082(02)00009-6","article-title":"Descending control of pain","volume":"66","author":"Millan","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1097\/SPC.0000000000000055","article-title":"Descending pain modulation and chronification of pain","volume":"8","author":"Ossipov","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/j.pain.0000000000000360","article-title":"Meta-analytic evidence for decreased heart rate variability in chronic pain implicating parasympathetic nervous system dysregulation","volume":"157","author":"Tracy","year":"2016","journal-title":"Pain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Forte, G., Troisi, G., Pazzaglia, M., Pascalis, V., and Casagrande, M. (2022). Heart Rate Variability and Pain: A Systematic Review. Brain Sci., 12.","DOI":"10.3390\/brainsci12020153"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.neuron.2018.11.009","article-title":"Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain","volume":"100","author":"Chen","year":"2018","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1007\/s13311-020-00905-7","article-title":"Central Nervous System Targets: Glial Cell Mechanisms in Chronic Pain","volume":"17","author":"Donnelly","year":"2020","journal-title":"Neurotherapeutics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.neubiorev.2019.10.007","article-title":"The interaction between stress and chronic pain through the lens of threat learning","volume":"107","author":"Timmers","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sanabria-Mazo, J.P., Colomer-Carbonell, A., Carmona-Cervell\u00f3, M., Feliu-Soler, A., Borr\u00e0s, X., Grasa, M., Esteve, M., Maes, M., Edo, S., and Sanz, A. (2022). Immune-inflammatory and hypothalamic-pituitary-adrenal axis biomarkers are altered in patients with non-specific low back pain: A systematic review. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.945513"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Armstrong, M., Castellanos, J., and Christie, D. (2024). Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies. Front. Pain Res., 5.","DOI":"10.3389\/fpain.2024.1346053"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00218-20","DOI":"10.1128\/mBio.00218-20","article-title":"Advances in Understanding the Human Urinary Microbiome and Its Potential Role in Urinary Tract Infection","volume":"11","author":"Neugent","year":"2020","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41385-022-00565-0","article-title":"The urothelium: A multi-faceted barrier against a harsh environment","volume":"15","author":"Jafari","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref_15","first-page":"S25","article-title":"Integrative control of the lower urinary tract: Preclinical perspective","volume":"147","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1152\/physrev.00030.2012","article-title":"Urothelial Signaling","volume":"93","author":"Birder","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s11033-025-10609-w","article-title":"Rewriting the urinary tract paradigm: The urobiome as a gatekeeper of host defense","volume":"52","author":"Pastuszka","year":"2025","journal-title":"Mol. Biol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120525","DOI":"10.1155\/2014\/120525","article-title":"The role(s) of cytokines\/chemokines in urinary bladder inflammation and dysfunction","volume":"2014","author":"Gonzalez","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Jhang, J.F., and Kuo, H.C. (2022). Can We Use Urinary Cytokine\/Chemokine Analysis in Discriminating Ulcer-Type Interstitial Cystitis\/Bladder Pain Syndrome?. Diagnostics, 12.","DOI":"10.3390\/diagnostics12051093"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jiang, Y.-H., Peng, C.-H., Liu, H.-T., and Kuo, H.-C. (2013). Increased Pro-Inflammatory Cytokines, C-Reactive Protein and Nerve Growth Factor Expressions in Serum of Patients with Interstitial Cystitis\/Bladder Pain Syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076779"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yu, W.R., Jiang, Y.H., Jhang, J.F., and Kuo, H.C. (2022). Use of Urinary Cytokine and Chemokine Levels for Identifying Bladder Conditions and Predicting Treatment Outcomes in Patients with Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051149"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/nau.25356","article-title":"The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women","volume":"43","author":"Smith","year":"2024","journal-title":"Neurourol. Urodyn."},{"key":"ref_23","unstructured":"Liao, L., and Madersbacher, H. (2023). Pain Bladder\/Pelvic Pain and Neurogenic Inflammation. Handbook of Neurourology: Theory and Practice, Springer Nature."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Roy, H.A., and Green, A.L. (2019). The Central Autonomic Network and Regulation of Bladder Function. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00535"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E448","DOI":"10.5489\/cuaj.7775","article-title":"The healthy urinary microbiome in asymptomatic participants in the MAPP Network Study: Relation to gender, age, and menopausal status","volume":"16","author":"Nickel","year":"2022","journal-title":"Can. Urol. Assoc. J."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jeries, L.M., Sysoeva, T.A., Karstens, L., and Kelly, M.S. (2024). Synthesis of current pediatric urinary microbiome research. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1396408"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01283-14","DOI":"10.1128\/mBio.01283-14","article-title":"The female urinary microbiome: A comparison of women with and without urgency urinary incontinence","volume":"5","author":"Pearce","year":"2014","journal-title":"mBio"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Perez-Carrasco, V., Soriano-Lerma, A., Soriano, M., Guti\u00e9rrez-Fern\u00e1ndez, J., and Garcia-Salcedo, J.A. (2021). Urinary Microbiome: Yin and Yang of the Urinary Tract. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.617002"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00105-25","DOI":"10.1128\/jb.00105-25","article-title":"The urinary microbiome: The next frontier of bacterial ecology","volume":"207","author":"Francis","year":"2025","journal-title":"J. Bacteriol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.tim.2018.11.003","article-title":"Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations","volume":"27","author":"Eisenhofer","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/s41564-025-02035-2","article-title":"Guidelines for preventing and reporting contamination in low-biomass microbiome studies","volume":"10","author":"Fierer","year":"2025","journal-title":"Nat. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11884-019-00543-6","article-title":"The Bladder is Not Sterile: An Update on the Urinary Microbiome","volume":"14","author":"Ackerman","year":"2019","journal-title":"Curr. Bladder Dysfunct. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"415","DOI":"10.3390\/jcm8030415","article-title":"A Culture-Independent Analysis of the Microbiota of Female Interstitial Cystitis\/Bladder Pain Syndrome Participants in the MAPP Research Network","volume":"8","author":"Nickel","year":"2019","journal-title":"J. Clin. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1111\/bju.16439","article-title":"The microbiota in patients with interstitial cystitis\/bladder pain syndrome: A systematic review","volume":"134","author":"Fu","year":"2024","journal-title":"BJU Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.urology.2016.02.043","article-title":"The Urinary Microbiome Differs Significantly Between Patients With Chronic Prostatitis\/Chronic Pelvic Pain Syndrome and Controls as Well as Between Patients With Different Clinical Phenotypes","volume":"92","author":"Shoskes","year":"2016","journal-title":"Urology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/nau.25550","article-title":"A systematic and comprehensive review of the role of microbiota in urinary chronic pelvic pain syndrome","volume":"43","author":"Hashemi","year":"2024","journal-title":"Neurourol. Urodyn."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Vocca, C., Abrego-Guandique, D.M., Cione, E., Rania, V., Marcian\u00f2, G., Palleria, C., Catarisano, L., Colosimo, M., La Cava, G., and Palumbo, I.M. (2025). Probiotics in the Management of Chronic Bacterial Prostatitis Patients: A Randomized, Double-Blind Trial to Evaluate a Possible Link Between Gut Microbiota Restoring and Symptom Relief. Microorganisms, 13.","DOI":"10.3390\/microorganisms13010130"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.1016\/S2665-9913(23)00324-7","article-title":"Nociceptive, neuropathic, or nociplastic low back pain? The low back pain phenotyping (BACPAP) consortium\u2019s international and multidisciplinary consensus recommendations","volume":"6","author":"Nijs","year":"2024","journal-title":"Lancet Rheumatol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lubomski, M., Xu, X., Holmes, A.J., Muller, S., Yang, J.Y.H., Davis, R.L., and Sue, C.M. (2022). The Gut Microbiome in Parkinson\u2019s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.875261"},{"key":"ref_40","first-page":"e088","article-title":"Validation of Digital Visual Analog Scale Pain Scoring With a Traditional Paper-based Visual Analog Scale in Adults","volume":"2","author":"Delgado","year":"2018","journal-title":"J. Am. Acad. Orthop. Surg. Glob. Res. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Straub, D., Blackwell, N., Langarica-Fuentes, A., Peltzer, A., Nahnsen, S., and Kleindienst, S. (2020). Interpretations of Environmental Microbial Community Studies Are Biased by the Selected 16S rRNA (Gene) Amplicon Sequencing Pipeline. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.550420"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"Ewels","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41592-018-0046-7","article-title":"Bioconda: Sustainable and comprehensive software distribution for the life sciences","volume":"15","author":"Dale","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1093\/bioinformatics\/btx192","article-title":"BioContainers: An open-source and community-driven framework for software standardization","volume":"33","author":"Uszkoreit","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: High-resolution sample inference from Illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"114250","DOI":"10.1016\/j.isci.2025.114250","article-title":"The neuroimmune axis and chronic pain disorders","volume":"29","author":"Feenstra","year":"2026","journal-title":"iScience"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Goudman, L., Demuyser, T., Pilitsis, J.G., Billot, M., Roulaud, M., Rigoard, P., and Moens, M. (2024). Gut dysbiosis in patients with chronic pain: A systematic review and meta-analysis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1342833"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.bja.2019.07.026","article-title":"Pain regulation by gut microbiota: Molecular mechanisms and therapeutic potential","volume":"123","author":"Guo","year":"2019","journal-title":"Br. J. Anaesth."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1097\/j.pain.0000000000001640","article-title":"Altered microbiome composition in individuals with fibromyalgia","volume":"160","author":"Minerbi","year":"2019","journal-title":"Pain"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, J., Zhu, N., Su, X., Gao, Y., and Yang, R. (2023). Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis. Cells, 12.","DOI":"10.3390\/cells12050793"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1038\/emm.2017.24","article-title":"The interplay between host immune cells and gut microbiota in chronic inflammatory diseases","volume":"49","author":"Kim","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-01743-1","article-title":"Microbiota\u2013gut\u2013brain axis and its therapeutic applications in neurodegenerative diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Song, W.J., Liu, X.Y., and He, L.Y. (2024). Research progress on the relationship between chronic prostatitis\/chronic pelvic pain syndrome and the microbiota of the reproductive system. Front. Cell Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1417276"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2014). Waste not, want not: Why rarefying microbiome data is inadmissible. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003531"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.1038\/s41467-020-17041-7","article-title":"Analysis of compositions of microbiomes with bias correction","volume":"11","author":"Lin","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"McMurdie, P.J., and Holmes, S. (2013). phyloseq: An R package for reproducible interactive analysis and graphics of microbiome census data. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061217"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41467-022-28034-z","article-title":"Microbiome differential abundance methods produce different results across 38 datasets","volume":"13","author":"Nearing","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nature11234","article-title":"Structure, function and diversity of the healthy human microbiome","volume":"486","author":"Huttenhower","year":"2012","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1126\/science.1177486","article-title":"Bacterial community variation in human body habitats across space and time","volume":"326","author":"Costello","year":"2009","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/rapm-2024-106030","article-title":"Innovations in acute and chronic pain biomarkers: Enhancing diagnosis and personalized therapy","volume":"50","author":"Mackey","year":"2025","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1093\/pm\/pnad009","article-title":"Toward the Identification of Distinct Phenotypes: Research Protocol for the Low Back Pain Biological, Biomechanical, and Behavioral (LB3P) Cohort Study and the BACPAC Mechanistic Research Center at the University of Pittsburgh","volume":"24","author":"Vo","year":"2023","journal-title":"Pain Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"111799","DOI":"10.1016\/j.jclinane.2025.111799","article-title":"The framework of chronic pain management: Redefining the outcomes","volume":"103","author":"Goudman","year":"2025","journal-title":"J. Clin. Anesth."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4931\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T05:05:38Z","timestamp":1782536738000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":67,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15134931"],"URL":"https:\/\/doi.org\/10.3390\/jcm15134931","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}