{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T22:46:28Z","timestamp":1785192388703,"version":"3.55.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Interstitial cystitis (IC) is a clinical syndrome characterized by frequency, urgency, and bladder pain or pelvic pain; however, the underlying pathophysiological mechanisms and diagnostic markers are unknown. In this study, microbiome and metabolome analysis were used to explain the urine signatures of IC patients. Urine samples from 20 IC patients and 22 control groups were analyzed by using 16S rRNA sequence and liquid chromatography coupled with mass spectrometry. Four opportunistic pathogen genera, including Serratia, Brevibacterium, Porphyromonas, and Citrobacter, were significantly upregulated in IC group. The altered metabolite signatures of the metabolome may be related to sphingosine metabolism, amino acid metabolism, and fatty acid biosynthesis. Meanwhile, the associations were observed between different metabolites and microbiomes of IC. The present study suggests that the combined signatures of IC in urine microbiome and metabolome may become its prospective diagnostic markers.<\/jats:p>","DOI":"10.3389\/fcimb.2021.711746","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:47:07Z","timestamp":1630694827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Combined Signature of the Urinary Microbiome and Metabolome in Patients With Interstitial Cystitis"],"prefix":"10.3389","volume":"11","author":[{"given":"Hewei","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nebiyu Elias","family":"Tamrat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiduo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengsen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liucheng","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baixin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqing","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1097\/aog.0000000000001892","article-title":"Urinary Microbiome and Cytokine Levels in Women With Interstitial Cystitis","volume":"129","author":"Abernethy","year":"2017","journal-title":"Obstet. Gynecol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.ejphar.2017.08.043","article-title":"Enhancement of S1P-Induced Contractile Response in Detrusor Smooth Muscle of Rats Having Cystitis","volume":"814","author":"Anjum","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1007\/s00345-019-03045-6","article-title":"Serum Sphingosine-1-Phosphate Levels in Bladder Pain Syndrome\/Interstitial Cystitis Patients: Could it Help in Diagnosis","volume":"38","author":"Asi","year":"2020","journal-title":"World J. Urol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1194\/jlr.R046300","article-title":"An Update on the Biology of Sphingosine 1-Phosphate Receptors","volume":"55","author":"Blaho","year":"2014","journal-title":"J. Lipid Res."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/srep26083","article-title":"Stool-Based Biomarkers of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"6","author":"Braundmeier-Fleming","year":"2016","journal-title":"Sci. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/nrurol.2016.262","article-title":"Microbiota in 2016: Associating Infection and Incontinence With the Female Urinary Microbiota","volume":"14","author":"Brubaker","year":"2017","journal-title":"Nat. Rev. Urol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"4605","DOI":"10.1242\/jcs.02637","article-title":"Sphingosine 1-Phosphate and Ceramide 1-Phosphate: Expanding Roles in Cell Signaling","volume":"118","author":"Chalfant","year":"2005","journal-title":"J. Cell Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.cell.2014.05.052","article-title":"Altering the Intestinal Microbiota During a Critical Developmental Window has Lasting Metabolic Consequences","volume":"158","author":"Cox","year":"2014","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/j.1365-2672.1973.tb04150.x","article-title":"Physicochemical Effects of Long Chain Fatty Acids on Bacterial Cells and Their Protoplasts","volume":"36","author":"Galbraith","year":"1973","journal-title":"J. Appl. Bacteriol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12882-020-01835-4","article-title":"Correction to: The Urinary Microbiome Shows Different Bacterial Genera in Renal Transplant Recipients and Non-Transplant Patients at Time of Acute Kidney Injury - a Pilot Study","volume":"21","author":"Gerges-Knafl","year":"2020","journal-title":"BMC Nephrol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.eururo.2011.07.069","article-title":"Contemporary Management of the Painful Bladder: A Systematic Review","volume":"61","author":"Giannantoni","year":"2012","journal-title":"Eur. Urol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1128\/jcm.02876-13","article-title":"Urine Is Not Sterile: Use of Enhanced Urine Culture Techniques to Detect Resident Bacterial Flora in the Adult Female Bladder","volume":"52","author":"Hilt","year":"2014","journal-title":"J. Clin. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1111\/j.1600-0765.2012.01501.x","article-title":"Predominant Immunoreactivity of Porphyromonas Gingivalis Heat Shock Protein in Autoimmune Diseases","volume":"47","author":"Jeong","year":"2012","journal-title":"J. Periodontal Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2119\/2006-00001.Kim","article-title":"Phytosphingosine Stimulates the Differentiation of Human Keratinocytes and Inhibits TPA-Induced Inflammatory Epidermal Hyperplasia in Hairless Mouse Skin","volume":"12","author":"Kim","year":"2006","journal-title":"Mol. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.ijantimicag.2005.08.020","article-title":"In Vitro Activity of Lauric Acid or Myristylamine in Combination With Six Antimicrobial Agents Against Methicillin-Resistant Staphylococcus Aureus (MRSA)","volume":"27","author":"Kitahara","year":"2006","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B16","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nrneurol.2015.197","article-title":"Pathogenesis of Parkinson Disease\u2013the Gut-Brain Axis and Environmental Factors","volume":"11","author":"Klingelhoefer","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jim.2015.02.003","article-title":"Citrobacter Rodentium-Induced Colitis: A Robust Model to Study Mucosal Immune Responses in the Gut","volume":"421","author":"Koroleva","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"B18","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1038\/nbt.2676","article-title":"Predictive Functional Profiling of Microbial Communities Using 16S rRNA Marker Gene Sequences","volume":"31","author":"Langille","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/nchembio.1535","article-title":"Gut Microbiota-Generated Metabolites in Animal Health and Disease","volume":"10","author":"Lee","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2013.00041","article-title":"The Human Urinary Microbiome; Bacterial DNA in Voided Urine of Asymptomatic Adults","volume":"3","author":"Lewis","year":"2013","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1038\/nrgastro.2012.152","article-title":"The Gut Microbiota in IBD","volume":"9","author":"Manichanh","year":"2012","journal-title":"Nat. Rev. Gastroenterol. Hepatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1349-7006.2005.00012.x","article-title":"Phytosphingosine Induced Mitochondria-Involved Apoptosis","volume":"96","author":"Nagahara","year":"2005","journal-title":"Cancer Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1434","DOI":"10.1194\/jlr.M600045-JLR200","article-title":"Lysophosphatidylethanolamine in Grifola Frondosa as a Neurotrophic Activator via Activation of MAPK","volume":"47","author":"Nishina","year":"2006","journal-title":"J. Lipid Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/sj.embor.7400731","article-title":"The Gut Flora as a Forgotten Organ","volume":"7","author":"O'Hara","year":"2006","journal-title":"EMBO Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4193","DOI":"10.1182\/blood-2007-09-115451","article-title":"Distinct Roles of Sphingosine Kinases 1 and 2 in Human Mast-Cell Functions","volume":"111","author":"Oskeritzian","year":"2008","journal-title":"Blood"},{"key":"B28","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.ebiom.2016.03.040","article-title":"Urinary Metabolomics Identifies a Molecular Correlate of Interstitial Cystitis\/Bladder Pain Syndrome in a Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Cohort","volume":"7","author":"Parker","year":"2016","journal-title":"EBioMedicine"},{"key":"B27","first-page":"878","article-title":"Phytosphingosine Induces Apoptotic Cell Death via Caspase 8 Activation and Bax Translocation in Human Cancer Cells","volume":"9","author":"Park","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"4411","DOI":"10.1016\/j.febslet.2007.08.014","article-title":"Lysophosphatidylethanolamine Stimulates Chemotactic Migration and Cellular Invasion in SK-OV3 Human Ovarian Cancer Cells: Involvement of Pertussis Toxin-Sensitive G-Protein Coupled Receptor","volume":"581","author":"Park","year":"2007","journal-title":"FEBS Lett."},{"key":"B29","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1467-2494.2007.00378.x","article-title":"Anti-Microbial and -Inflammatory Activity and Efficacy of Phytosphingosine: An In\u00a0Vitro and In Vivo Study Addressing Acne Vulgaris","volume":"29","author":"Pavicic","year":"2007","journal-title":"Int. J. Cosmet Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e01283","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":"B31","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1172\/jci76369","article-title":"Emerging Biology of Sphingosine-1-Phosphate: Its Role in Pathogenesis and Therapy","volume":"125","author":"Proia","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1300\/j013v31n04_05","article-title":"Pain and Depression Experienced by Women With Interstitial Cystitis","volume":"31","author":"Rabin","year":"2000","journal-title":"Women Health"},{"key":"B33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12944-018-0665-0","article-title":"Lipidomic Analysis of Serum Samples From Migraine Patients","volume":"17","author":"Ren","year":"2018","journal-title":"Lipids Health Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"5003","DOI":"10.3892\/mmr.2020.11627","article-title":"Metabolomic and Lipidomic Approaches to Identify Biomarkers for Bladder Cancer and Interstitial Cystitis (Review)","volume":"22","author":"Shahid","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.juro.2017.08.001","article-title":"Profiling the Urinary Microbiome in Men With Positive Versus Negative Biopsies for Prostate Cancer","volume":"199","author":"Shrestha","year":"2018","journal-title":"J. Urol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-12-205","article-title":"Alterations of Microbiota in Urine From Women With Interstitial Cystitis","volume":"12","author":"Siddiqui","year":"2012","journal-title":"BMC Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1681\/asn.2015010107","article-title":"Urine Metabolite Profiles Predictive of Human Kidney Allograft Status","volume":"27","author":"Suhre","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7490452","article-title":"Effects of Lactobacillus Gasseri OLL2716 on Helicobacter Pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial","volume":"2016","author":"Takagi","year":"2016","journal-title":"Gastroenterol. Res. Pract."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1007\/s11255-015-1108-8","article-title":"Influence of Polyunsaturated Fatty Acids on Urologic Inflammation","volume":"47","author":"Tamma","year":"2015","journal-title":"Int. Urol Nephrol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature18847","article-title":"The Microbiome and Innate Immunity","volume":"535","author":"Thaiss","year":"2016","journal-title":"Nature"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2016.07.049","article-title":"Evaluation of the Urinary Microbiota of Women With Uncomplicated Stress Urinary Incontinence","volume":"216","author":"Thomas-White","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1128\/jcm.05852-11","article-title":"Evidence of Uncultivated Bacteria in the Adult Female Bladder","volume":"50","author":"Wolfe","year":"2012","journal-title":"J. Clin. Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.711746\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T18:47:10Z","timestamp":1630694830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.711746\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":43,"alternative-id":["10.3389\/fcimb.2021.711746"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.711746","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]},"article-number":"711746"}}