Oral Lactobacillus crispatus M247 as add-on prophylaxis for recurrent cystitis in women: a randomized pilot trial

Background Recurrent cystitis is common in women and drives repeated antibiotic exposure. We evaluated whether women supplemented orally with Lactobacillus crispatus M247 alongside Enterococcus faecium L3 plus Bifidobacterium animalis subsp. lactis BB-12 experienced fewer symptomatic cystitis recurrences than those receiving L3 plus BB-12 alone. Methods In this prospective, randomized, controlled, open-label, single-center exploratory pilot trial, 84 women with recurrent uncomplicated cystitis were allocated 1:1 to receive L. crispatus M247 for 90 days plus E. faecium L3 and B. animalis subsp. lactis BB-12 during the first 30 days (M247 add-on) or L3 plus BB-12 alone for 30 days. The primary outcome was the cumulative number of symptomatic cystitis recurrences per participant through 12 months after randomization. Recurrence status, patient-reported outcomes, adherence, tolerability, and safety were also assessed. Results All participants completed follow-up. By month 12, 19 recurrences occurred with M247 add-on and 46 with L3 plus BB-12 (0.45 ± 1.09 vs. 1.10 ± 1.56 episodes per participant; 58.7% relative reduction; p = 0.037). Seven of 42 women (16.7%) versus 15 of 42 (35.7%) experienced at least one recurrence, an absolute risk reduction of 19.0 percentage points (95% CI, 0.2–36.3; p = 0.047). At month 3, there were 2 versus 12 cumulative episodes (83.3% relative reduction; p = 0.022) and 2/42 (4.8%) versus 9/42 (21.4%) women with at least one recurrence (absolute risk reduction, 16.7 percentage points; 95% CI, 2.0–31.6; p = 0.024). Exploratory patient-reported findings included a lower Pelvic Pain and Urgency/Frequency (PUF) score at month 3 in the M247 add-on group (mean difference, −2.18 points; 95% CI, −3.12 to −1.24). All participants achieved at least 90% adherence; no serious adverse events or treatment discontinuations occurred. Conclusion In this exploratory pilot trial, M247 add-on supplementation was associated with a lower symptomatic cystitis recurrence burden than L3 plus BB-12 alone. Findings concerning urinary symptoms, sexual function, and quality of life are exploratory and remain susceptible to contextual and expectation-related effects. Confirmation in larger, double-blind, placebo-controlled multicenter trials is required. Clinical trial registration The trial is registered at ClinicalTrials.gov under identifier NCT06857565: https://clinicaltrials.gov/study/NCT06857565 .