{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:29:13Z","timestamp":1773264553695,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["101034270"],"award-info":[{"award-number":["101034270"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Urinary tract infections (UTIs) impose a substantial burden on women\u2019s health, and probiotics have emerged as an alternative strategy to support urogenital wellbeing. This study evaluated the antimicrobial properties of Limosilactobacillus reuteri 3613-1 and its ability to improve UTI outcomes in women with a history of recurrent uncomplicated UTIs. In vitro assays demonstrated that L. reuteri 3613-1 inhibited the growth of Escherichia coli isolates and proved superior inhibition of Gardnerella vaginalis and Candida albicans compared with a comparator L. reuteri strain, supported by confirmed reuterin production and genomic profiling. A randomized, double-blind, placebo-controlled clinical trial (n = 130) assessed daily supplementation with L. reuteri 3613-1 for 24 weeks. While the proportion, frequency, and intensity of confirmed UTIs did not differ significantly between groups, L. reuteri 3613-1 delayed the onset of the first UTI, reaching significance in participants with suspected while unconfirmed UTIs. Vaginal pH and vaginal microbiome composition remained stable and comparable between groups across the intervention. The product was safe and well tolerated. Overall, L. reuteri 3613-1 shows promise as a probiotic candidate with antimicrobial activity and potential to delay symptom onset in women susceptible to recurrent UTIs, warranting further investigation in larger studies.<\/jats:p>","DOI":"10.3390\/microorganisms14030615","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T15:49:42Z","timestamp":1773071382000},"page":"615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limosilactobacillus reuteri 3613-1 Delays Onset of Unconfirmed Urinary Tract Infections in Otherwise Healthy Women"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8558-6640","authenticated-orcid":false,"given":"Valentine","family":"Turpin","sequence":"first","affiliation":[{"name":"APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland"},{"name":"Department of Anatomy and Neuroscience, School of Medicine, University College Cork, T12 XF62 Cork, Ireland"},{"name":"Atlantia Food Clinical Trials, Heron House Offices, Blackpool, T23 R50R Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Kakilla","sequence":"additional","affiliation":[{"name":"Atlantia Food Clinical Trials, Heron House Offices, Blackpool, T23 R50R Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Foote","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., W227N752 Westmound Dr., Waukesha, WI 53186, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Chen","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., 469 North Harrison Street, Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hooper","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., 469 North Harrison Street, Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wafaa","family":"Ayad","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., 469 North Harrison Street, Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annahita","family":"Ghassemi","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., 469 North Harrison Street, Princeton, NJ 08540, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Verb Biotics, 701 W. Main St. Suite 200, Durham, NC 27701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran","family":"Rea","sequence":"additional","affiliation":[{"name":"Atlantia Food Clinical Trials, Heron House Offices, Blackpool, T23 R50R Cork, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Wescott","sequence":"additional","affiliation":[{"name":"Church & Dwight Co., Inc., W227N752 Westmound Dr., Waukesha, WI 53186, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s00404-019-05256-z","article-title":"Prevention and Treatment of Uncomplicated Lower Urinary Tract Infections in the Era of Increasing Antimicrobial Resistance\u2014Non-Antibiotic Approaches: A Systemic Review","volume":"300","author":"Wawrysiuk","year":"2019","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1007\/s00345-019-03071-4","article-title":"Epidemiology of Urological Infections: A Global Burden","volume":"38","author":"Murt","year":"2020","journal-title":"World J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mancuso, G., Midiri, A., Gerace, E., Marra, M., Zummo, S., and Biondo, C. (2023). Urinary Tract Infections: The Current Scenario and Future Prospects. Pathogens, 12.","DOI":"10.3390\/pathogens12040623"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1177\/1756287219832172","article-title":"An Introduction to the Epidemiology and Burden of Urinary Tract Infections","volume":"11","author":"Medina","year":"2019","journal-title":"Ther. Adv. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.chom.2022.04.008","article-title":"Persisting Uropathogenic Escherichia coli Lineages Show Signatures of Niche-Specific within-Host Adaptation Mediated by Mobile Genetic Elements","volume":"30","author":"Choi","year":"2022","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41564-022-01107-x","article-title":"Longitudinal Multi-Omics Analyses Link Gut Microbiome Dysbiosis with Recurrent Urinary Tract Infections in Women","volume":"7","author":"Worby","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00460-13","DOI":"10.1128\/mBio.00460-13","article-title":"Influence of Vaginal Bacteria and D- and L-Lactic Acid Isomers on Vaginal Extracellular Matrix Metalloproteinase Inducer: Implications for Protection against Upper Genital Tract Infections","volume":"4","author":"Witkin","year":"2013","journal-title":"mBio"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1111\/1471-0528.14390","article-title":"Why Do Lactobacilli Dominate the Human Vaginal Microbiota?","volume":"124","author":"Witkin","year":"2017","journal-title":"BJOG"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"UTI-0025-2016","DOI":"10.1128\/microbiolspec.UTI-0025-2016","article-title":"The Vaginal Microbiota and Urinary Tract Infection","volume":"4","author":"Stapleton","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Baimakhanova, B., Sadanov, A., Trenozhnikova, L., Balgimbaeva, A., Baimakhanova, G., Orasymbet, S., Tleubekova, D., Amangeldi, A., Turlybaeva, Z., and Nurgaliyeva, Z. (2025). Understanding the Burden and Management of Urinary Tract Infections in Women. Diseases, 13.","DOI":"10.3390\/diseases13020059"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, S., Reid, G., Challis, J.R.G., Gloor, G.B., Asztalos, E., Money, D., Seney, S., and Bocking, A.D. (2020). Effect of Oral Probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the Vaginal Microbiota, Cytokines and Chemokines in Pregnant Women. Nutrients, 12.","DOI":"10.3390\/nu12020368"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.tjog.2016.06.003","article-title":"Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to Reduce Group B Streptococcus Colonization in Pregnant Women: A Randomized Controlled Trial","volume":"55","author":"Ho","year":"2016","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1093\/cid\/cir183","article-title":"Randomized, Placebo-Controlled Phase 2 Trial of a Lactobacillus crispatus Probiotic given Intravaginally for Prevention of Recurrent Urinary Tract Infection","volume":"52","author":"Stapleton","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yefet, E., Colodner, R., Strauss, M., Zeletova, Y.G., and Nachum, Z. (2020). A Randomized Controlled Open Label Crossover Trial to Study Vaginal Colonization of Orally Administered Lactobacillus reuteri Rc-14 and Lactobacillus rhamnosus Gr-1 in Pregnant Women at High Risk for Preterm Labor. Nutrients, 12.","DOI":"10.3390\/nu12041141"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1128\/JCM.01710-09","article-title":"Comparison of self-collected and physician-collected vaginal swabs for microbiome analysis","volume":"48","author":"Forney","year":"2010","journal-title":"J. Clin. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/2327-6924.12110","article-title":"Managing Uncomplicated Recurrent Urinary Tract Infections in Reproductive Aged Women: A Primary Care Approach","volume":"26","author":"Zak","year":"2014","journal-title":"J. Am. Assoc. Nurse Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1097\/JU.0000000000001383","article-title":"Warmer Weather and the Risk of Urinary Tract Infections in Women","volume":"205","author":"Simmering","year":"2021","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejogrb.2008.06.003","article-title":"Randomized, Double-Blind, Placebo-Controlled Study of Oral Lactobacilli to Improve the Vaginal Flora of Postmenopausal Women","volume":"141","author":"Petricevic","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/1471-0528.15675","article-title":"Effects of Oral Probiotic Supplements on Vaginal Microbiota during Pregnancy: A Randomised, Double-Blind, Placebo-Controlled Trial with Microbiome Analysis","volume":"127","author":"Husain","year":"2020","journal-title":"BJOG"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1111\/apm.13261","article-title":"Vaginal Microbiome Following Orally Administered Probiotic","volume":"130","author":"Hertz","year":"2022","journal-title":"Apmis"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Romeo, M., D\u2019Urso, F., Ciccarese, G., Di Gaudio, F., and Broccolo, F. (2024). Exploring Oral and Vaginal Probiotic Solutions for Women\u2019s Health from Puberty to Menopause: A Narrative Review. Microorganisms, 12.","DOI":"10.3390\/microorganisms12081614"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11934-022-01085-x","article-title":"Role of Probiotics for Recurrent UTIs in the Twenty-First Century: A Systematic Review of Literature","volume":"23","author":"New","year":"2022","journal-title":"Curr. Urol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1153894","DOI":"10.3389\/fcimb.2023.1153894","article-title":"Use of Probiotic Lactobacilli in the Treatment of Vaginal Infections: In Vitro and in Vivo Investigations","volume":"13","author":"Liu","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41522-025-00839-y","article-title":"Microbial Regulators of Physiological and Reproductive Health in Women of Reproductive Age: Their Local, Proximal and Distal Regulatory Roles","volume":"11","author":"Cheng","year":"2025","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Takada, K. (2025). IgA and the Gut-Vagina Axis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1547303"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e14562","DOI":"10.1016\/j.heliyon.2023.e14562","article-title":"Microbiota Metabolites in the Female Reproductive System: Focused on the Short-Chain Fatty Acids","volume":"9","author":"Mirzaei","year":"2023","journal-title":"Heliyon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S234","DOI":"10.1097\/MCG.0b013e31817f1298","article-title":"Probiotic Lactobacilli for Urogenital Health in Women","volume":"42","author":"Reid","year":"2008","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.euros.2022.07.009","article-title":"Adherence to European Association of Urology Guidelines and State of the Art of Glycosaminoglycan Therapy for the Management of Urinary Tract Infections: A Narrative Review and Expert Meeting Report","volume":"44","author":"Bonkat","year":"2022","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1001\/archinternmed.2012.777","article-title":"Lactobacilli vs antibiotics to prevent urinary tract infections: A randomized, double-blind, noninferiority trial in postmenopausal women","volume":"172","author":"Beerepoot","year":"2012","journal-title":"Arch. Intern. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.idc.2013.10.001","article-title":"Prevention of recurrent urinary tract infections in women: Antimicrobial and nonantimicrobial strategies","volume":"28","author":"Geerlings","year":"2014","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_31","first-page":"CD008772","article-title":"Probiotics for preventing urinary tract infections in adults and children","volume":"2015","author":"Schwenger","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nelwan, E.J., Herdiman, A., Kalaij, A.G.I., Lauditta, R.K., Yusuf, S.M., and Suarthana, E. (2024). Role of probiotic as adjuvant in treating various infections: A systematic review and meta-analysis. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-09259-3"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/3\/615\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:27:52Z","timestamp":1773206872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/3\/615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":32,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["microorganisms14030615"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14030615","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]}}}