Oral Administration of the Probiotic <em>Lacticaseibacillus rhamnosus</em> CA15 in a Large Cohort of Women with Bacterial Vaginosis and Mixed Vaginitis: Clinical Evidence from a Randomized, Double-Blind, Placebo-Controlled Study

Background/Objectives: Lactobacilli are recognized as indicators of vaginal health and probiotics represent a valuable approach to maintain or restore the homeostasis of the vaginal ecosystem. A randomized double-blind placebo-controlled study was conducted to confirm the health benefits of the orally administered probiotic Lacticaseibacillus rhamnosus CA15 strain, compared to placebo, in a large cohort of women with bacterial vaginosis (BV) and mixed vaginitis (MV), mainly related to mild aerobic vaginitis (AV) and vulvovaginal candidiasis (VVC). Methods: Two-hundred women, exhibiting signs and symptoms of bacterial vaginosis (BV) and mixed vaginitis (MV), were recruited, and randomly assigned in a 1:1 ratio to receive for 10 days, oral capsules containing 1x1010 colony forming units (cfu) of the L. rhamnosus CA15 strain (Active group) or a placebo (Placebo group). Clinical (leucorrhoea, burning, itching, vulvovaginal erythema/oedema, subjective vaginal discomfort, Nugent score, Amsel criteria, and Lactobacillary grade) and microbiological parameters (vaginal microbiota composition) were assessed at baseline (T0), 10 days after the start of the treatment (T1), and 30 days post-treatment (T2). In addition, quality of life was evaluated at baseline and 30 days post-treatment using the WHOQOL-BREF questionnaire. The study protocol was registered on clinicaltrials.gov (ID: NCT05796921). Results: The oral administration of the L. rhamnosus CA15 strain resulted in significant improvements in clinical characteristics of BV (leucorrhea, Nugent score, and Amsel criteria), AV (lactobacillary grade, discharge, and subjective vaginal discomfort), and VVC (leucorrhea, burning, itching, vulvovaginal erythema/oedema, and subjective vaginal discomfort) as well as changes in the vaginal microbiota composition. Furthermore, participants allocated to the Active group reported enhancements in physical and psychological health, social relations, environment, and overall quality of life. No significant changes in clinical and microbiological parameters nor in quality of life, were observed in the Placebo group. Conclusions: The randomized double-blind placebo-controlled study conducted on a large cohort of women highlighted the therapeutic value of the L. rhamnosus CA15 in the management of BV occurring with mixed infections. This probiotic strain represents a safe and effective strategy for restoring the balance of the vaginal microbiota, alleviating clinical symptoms, and enhancing the quality of life of subjects with co-occurring vaginal infections. This finding offers new perspectives for the treatment and prevention of common gynecological disorders.