Effect of an Add-On Multi-Strain Probiotic Formulation in the Prevention of Recurrent Urinary Tract Infections: A Double-Blind Randomized Placebo-Controlled Trial

Abstract

Urinary tract infections (UTIs) present a significant health challenge for women globally, particularly due to high recurrence rates. This randomized, double-blinded, placebo-controlled study conducted at AIIMS Bhubaneswar, India, evaluated the effectiveness of a multi-strain lactobacilli probiotic formulation as an adjunct to standard antibiotic therapy in preventing recurrent UTIs. Fifty-one adult women (18–50 years) with recurrent UTIs received either the probiotic or a placebo for 24 weeks. The primary outcome was UTI recurrence, while secondary outcomes included the number of UTI episodes and changes in urinary nerve growth factor (NGF) and serum macrophage colony-stimulating factor (M-CSF) levels. The results showed a significant reduction in UTI recurrence in the probiotic group, with 75% remaining recurrence-free, compared to 33% in the placebo group (p = 0.007). The relative risk for recurrence absence was 2.67 (95% CI: 1.19–5.99). Although the mean number of UTI episodes decreased in the probiotic group, the difference was not statistically significant (p = 0.379). The urinary NGF and serum M-CSF levels significantly decreased from baseline in both groups, but there were no significant differences between them. This study suggests probiotics may be a valuable adjunct therapy for preventing recurrent UTIs.

1. Introduction

Urinary Tract Infections (UTIs) represent a pervasive and persistent health concern worldwide, affecting individuals across all age groups, genders, and demographics. They account for millions of healthcare visits and hospitalizations annually, contributing significantly to the global disease burden. The high prevalence and recurrence rates of UTIs impose substantial economic costs on healthcare systems and create considerable challenges for both prevention and treatment. The prevalence of UTIs is particularly pronounced in women globally, with estimates suggesting that up to 60% will experience at least one UTI episode during their lifetime [1]. In addition to an increase observed in young women, the incidence of UTIs continues to rise with age. For women over 65 years old, the prevalence is about 20%, compared to 11% in the general population [2].

The conventional UTI treatment mainly involves antibiotic therapy, which, despite effectively eradicating bacterial pathogens, has significant drawbacks. While antibiotics serve as the primary line of defense, their repeated use has led to complications, including adverse effects on the gut microbiota and the rise of multidrug-resistant bacteria. This not only compromises the efficacy of treatment for UTI patients but also has broader implications for antimicrobial resistance on a global scale. Indiscriminate antibiotic use has led to the rise of antibiotic-resistant strains, posing a major public health threat [3]. Moreover, UTI recurrence rates are high, highlighting the need for alternative management and prevention strategies.

The human microbiome, a complex community of microorganisms, is crucial for health and disease prevention [4]. In the urogenital tract, a balanced microbial ecosystem defends against pathogens, strengthens the mucosal barrier, and prevents infections [5]. In women, the composition of the vaginal and urogenital microbiota plays an essential role in providing a natural defense against urinary pathogens. Imbalances in these microbiotas, often caused by antibiotic treatments or hormonal changes, can disrupt the body’s natural defenses, increasing susceptibility to infection. Disruptions to this microbial equilibrium, often induced by antibiotics, leave individuals susceptible to recurrent UTIs. Disruptions to microbial equilibrium caused by antibiotic treatment increase the susceptibility to recurrent UTIs.

Probiotics, traditionally associated with gut health, have emerged as potential candidates for restoring and maintaining microbial equilibrium across various anatomical niches, including the urogenital tract. By restoring beneficial bacteria, probiotics may provide a promising alternative to long-term antibiotic prophylaxis in recurrent UTIs. Their potential to modulate the composition and function of resident microbiota, bolstering the host’s innate defenses, proposes a rationale for investigating their efficacy in recurrent UTIs. Probiotic microorganisms combat infections, modulate the host immune response, and foster an environment favorable to beneficial bacteria [6]. Research suggests that probiotics, particularly Lactobacillus species, can help replenish beneficial bacteria, creating an environment that discourages pathogenic colonization and growth.

Specific Lactobacillus species, such as Lactobacillus rhamnosus and Lactobacillus reuteri, have demonstrated growth inhibition and adhesion of prevalent uropathogens like Escherichia coli [7]. These probiotic organisms exert an antagonistic effect on pathogens by competitive exclusion and production of antimicrobial substances, such as organic acids and bacteriocins, preventing their establishment (biofilm formation) on uroepithelial surfaces [8]. Probiotics also interact with the host immune system, regulating cytokine and chemokine production, contributing to a balanced immune response [9]. By enhancing both innate and adaptive immune mechanisms, probiotics can potentially provide a long-term defense mechanism against the recurrence of UTIs.

In addition to immune modulation, probiotics can enhance immune cell activity and promote an anti-inflammatory environment, potentially fortifying the urogenital mucosa against recurrent infections. The short-chain fatty acids (SCFAs) produced by probiotics further support mucosal defense by enhancing the expression of tight junction proteins (occludin and claudin), thus strengthening the epithelial barrier. Moreover, probiotics contribute to mucosal integrity by promoting the production of mucin and reinforcing tight junctions between epithelial cells [10]. These mechanisms contribute to a robust and resilient mucosal layer that is crucial for preventing bacterial infiltration and colonization in the urinary tract. An intact and resilient mucosal barrier is crucial for preventing the colonization and spread of uropathogens within the urinary tract.

A number of clinical trials have sought to assess the efficacy and safety of probiotics in the treatment of UTIs. While some studies have reported promising outcomes, demonstrating a reduction in UTI recurrence rates and improved microbial profiles [11,12,13], others present conflicting results, underscoring the complexity of this field [14,15,16]. Despite these promising findings, there remains a need for large-scale, high-quality randomized controlled trials to establish standardized protocols for probiotic therapy in UTIs. Further, understanding which probiotic strains are most effective in different populations, including by age or comorbid conditions, is vital.

One of the challenges in interpreting clinical evidence lies in the considerable heterogeneity among probiotic strains. Additionally, establishing optimal dosage regimens remains an area of active investigation, as the therapeutic efficacy of probiotics may be influenced by factors such as colonization efficiency and persistence within the urogenital tract. The dosage and duration of probiotic therapy, as well as strain selection, are critical factors that may influence patient outcomes yet remain largely underexplored in the current literature. Moreover, there is insufficient evidence on the combined effect of probiotics along with antibiotics on the prevention of UTIs, especially in the Indian context.

As the effects of probiotics are strain-specific, the aim of this study was to assess the effect of add-on probiotics in adult women with recurrent UTI (rUTI). A multi-strain probiotic formulation was chosen to leverage potential synergistic effects among strains, with each selected based on in vitro evidence of antipathogenic activity, including adhesion inhibition, antimicrobial production, and immune modulation. The strains in the multi-strain probiotic formulation were selected based on their antipathogenic activity, as determined through in vitro studies. Apart from assessing the incidence of UTIs in both the probiotic and placebo-treated groups, this study also measured serum macrophage colony-stimulating factor (M-CSF) and urinary nerve growth factor (NGF), which are suggested biomarkers of UTI.

2. Materials and Methods

2.1. Study Design

This double blind, randomized, parallel group, placebo-controlled study was conducted at the outpatient department of the Obstetrics & Gynecology and Pharmacology Department, All India Institute of Medical Sciences (AIIMS), Bhubaneshwar, India, between February 2019 and September 2023. This trial was initiated following registration with the CTRI (CTRI/2019/04/018434). This study was initiated after obtaining approval from the Institute Ethics Committee, All India Institute of Medical Sciences, Bhubaneswar (T/EMF/Pharma/18/22). This study followed the Declaration of Helsinki, Good Clinical Practices guidelines and ICMR’s Ethical Guidelines for Biomedical and Health Research involving Human Participants.

2.2. Participants

The participants were women aged 18–50 years who had not attained menopause and were experiencing an ongoing episode of recurrent urinary tract infection (UTI). Recurrent UTI was defined as either ≥2 symptomatic, culture-confirmed UTIs within the past 6 months or ≥3 symptomatic, culture-proven UTIs over the past 12 months. The participants were included after obtaining their consent to participate willingly. Women with the following conditions were excluded from this study: polycystic disease; interstitial cystitis; previous urological surgery; history of stones or anatomical abnormalities of the urinary tract; pregnant or breastfeeding women or those planning a pregnancy within the next 6 months; known allergies or intolerance to any study products; history of renal stones and/or renal transplantation; any immunosuppressive disease or other medical conditions that could potentially interfere with outcomes; current use of corticosteroids, anticoagulants, antidepressants or mood-stabilizing medications or other medications that may interact with the supplement; and those with the requirement of catheterization. All participants were thoroughly informed about the purpose of this trial as well as the benefits and potential risks associated. They were assured of confidentiality and their freedom to withdraw from this study.

2.3. Interventions

Standard antibiotic treatment: The choice of antibiotics for standard treatment depended on the specific bacteria present and their susceptibility to different antibiotics. The majority of patients were tested positive for E. coli and were prescribed antibiotics according to their culture and sensitivity test results. In the probiotic group, Nitrofurantonin (100 mg) was administered to 56% of patients twice daily, Ofloxacin (500 mg) was administered to 24% of the patients twice daily, and the remaining patients received Cefixime (200 mg) twice daily. Meanwhile, in the placebo group, 50% were given Nitrofurantoin and 27% were prescribed Ofloxacin, and the remaining patients received cefixime. The antibiotics were prescribed for a period of 7–10 days as per treatment guidelines for each episode of infection.

2.4. Investigational Drugs (Probiotics and Placebo) as Adjunct Therapy

Probiotic and placebo capsules were provided by Unique Biotech Limited, Hyderabad, Telangana, India. The probiotic group received multi-strain probiotic oral capsules of 10 billion colony-forming units (CFU) comprising Lactobacillus acidophilus UBLA-34 (2.0 billion), L. rhamnosus UBLR-58 (2.0 billion), L. reuteri UBLRu-87 (2.0 billion), L. plantarum UBLP-40 (1.0 billion), L. casei UBLC-42 (1.0 billion), L. fermentum UBLF-31 (1.0 billion), Bifidobacterium bifidum UBBB-55 (1.0 billion), and fructo-oligosaccharide (100 mg). Participants in the placebo group received identical-looking capsules containing only excipients, without any active ingredients. Both the placebo and probiotic groups received one capsule twice a day for a period of 24 weeks. The patients were advised to maintain a gap of at least 2 h between the antibiotic and the probiotic or the placebo intake, preferably antibiotic followed by the probiotic/placebo capsules in that order. Patients received a three-month supply of probiotic and placebo capsules and were instructed to keep and return all capsule strips at follow-up visits. Adherence to the study medication was monitored by pill counting.

2.5. Study Follow-Up Visits and Treatments

In addition to the initial visit upon recruitment (baseline visit), the patients were scheduled to return for follow-up visits at 12 weeks and 24 weeks. They were also instructed to visit if they experienced any episodes of UTI between the scheduled follow-up visits.

2.6. Outcomes

The primary outcome was to evaluate the variation in the incidence of urinary tract infection in women receiving probiotic therapy compared to those receiving a placebo treatment over a 24-week period. The secondary outcomes included comparing the mean number of UTI episodes in patients with recurrence, estimating serum macrophage colony-stimulating factor (M-CSF) and urine nerve growth factor (NGF), and assessing any potential adverse events between the groups. During the screening visit, the urine samples were collected from the subjects for microbial culture and sensitivity tests alongside the acquisition of demographic data. Following enrolment, a 2 mL random blood sample was collected at baseline and during the 6-month visits to quantify serum macrophage colony-stimulating factor (M-CSF). The serum from the blood samples was extracted and stored at −80 °C for subsequent analysis.

2.7. Sample Size

Assuming a 15% reduction in the recurrence rate due to probiotic use and assuming the placebo control group will have no change in the recurrence rate of developing UTI, a sample size of 41 is required in each group, making a total of 82 cases. This sample powered to 80% to detect the difference, allowing a type-I error of 5%. However, we could recruit only 51 patients due to COVID-19 pandemic restrictions. We performed a post hoc power analysis to check if the study results were adequately powered to draw conclusions.

2.8. Randomization and Blinding

Eligible participants were randomly allocated into two groups with a 1:1 allocation ratio to receive either probiotic or a placebo orally for a duration of 24 weeks. Any case of UTI during the study period was treated with empiric antibiotics, which, if required, was changed as per the culture and sensitivity report.

Participants were randomized by computer-generated block randomization (blocks of four). The investigator involved in the randomization process was not involved in recruiting the patients. Allocation concealment was ensured by dispensing the probiotic or placebo capsules in identical looking sequentially numbered boxes which were assigned to the patients based on the randomization numbers. Both the investigator and study participants were blinded to the treatment assignments.

2.9. Estimation of Urinary Nerve Growth Factor

Urine samples were collected at full bladder capacity and were analyzed for urinary nerve growth factor (uNGF) [17] using a Human NGF (Nerve Growth Factor) Elisa Kit, ElabScience, Houston, TX, USA. The optical densities were measured at a wavelength of 450 nm. uNGF concentrations were determined from the standard curve.

2.10. Quantification of Serum M-CSF

Blood samples were collected, and serum was separated, aliquoted, and stored at −20 °C until further analysis. M-CSF levels [18,19] were determined using sandwich enzyme immunoassay with a human M-CSF (Macrophage Colony Stimulating Factor 1), ELISA Kit, ElabScience, USA.

2.11. Statistical Analysis

Continuous data were expressed as mean ± SD. Categorical data were expressed as proportions. Baseline data were analyzed using an independent t-test for continuous variables, and the chi-square test was used for categorical data. The data for change from baseline were analyzed using a paired t-test within the group, and differences between the groups were analyzed using an independent t-test. Both per-protocol and modified intention-to-treat analyses (mITT) were performed. Patients receiving at least one treatment dose were considered for mITT, and multiple imputations were performed to replace missing data. The patients who adhered to the study protocol and completed all scheduled visits were considered for per-protocol analysis. All analyses were performed using R version 4.3.0. p < 0.05 was considered statistically significant.

3. Results

Out of 87 individuals with urinary tract infections screened, 51 women were enrolled in this study. All the patients received standard antibiotic therapy. After enrolment, 25 patients were randomized to receive add-on probiotic capsules, and 26 patients were randomized to receive placebo capsules. Five patients were lost to follow-up in the add-on probiotic group, while two patients were lost to follow in the placebo group. These patients were reluctant to come for follow-up visits as they did not experience any episode of UTI after the baseline visit (Figure 1). The mean age of the subjects at baseline was 34.76 ± 6.88 years and 31.31 ± 6.41 years in probiotic and placebo groups, respectively. All subjects in this study were of Indian origin (

Table 1. Demographic and clinical characteristics at baseline.

Parameters	Probiotic Group (n = 25)	Placebo Group (n = 26)	p-Value *
Age (years)	34.76 ± 6.88	31.31 ± 6.41	0.070
Weight (kg)	41.2 ± 8.85	39.23 ± 11.25	0.489
Height (cm)	149.08 ± 10.14	150.15 ± 9.15	0.693
Education Uneducated: Primary: Secondary: Graduation	5:11:6:3	5:9:8:4	0.894 #
Rural: Urban	12:13	8:18	0.330 #
Number of UTI episodes in past 6 months (median)	3 (2–5)	3 (2–6)	0.378
Antibiotic use Nitrofurantoin: Ofloxacin: Cefixime	14:6:5	13:7:6	0.911 #
Urine NGF	37.56 ± 9.37	36.25 ± 7.27	0.578
Serum M-CSF	35.61 ± 7.67	31.52 ± 10.79	0.125

* Independent t-test; ^# Chi-square/Fischer exact test.

).

3.1. Incidence and Frequency of Urinary Tract Infections

Among the individuals receiving probiotics in a group of twenty patients, fifteen (75%) showed no recurrence of UTI, whereas only eight (33.3%) out of twenty-four patients in the placebo group remained recurrence-free. The relative risk for the absence of recurrences was 2.67 (95% CI: 1.19 to 5.99; p = 0.007), indicating statistical significance. The risk difference between the experimental and control groups was also 0.417 (95% CI: 0.149 to 0.684), which also achieved statistical significance. The outcomes from the modified intention-to-treat analysis closely mirrored those of the per-protocol analysis. The relative risk for recurrence was 2.11 (95% CI: 1.66 to 2.69, p < 0.001), and the risk difference was 0.35 (95% CI: 0.25 to 0.45). The mean number of UTI episodes in the patients with recurrence belonging to probiotic and placebo groups were 1.75 ± 1.48 and 2.28 ± 0.95, respectively, at 24 weeks. There was no statistically significant difference between the groups (mean difference: 0.80; 95% CI: −1.81 to 0.75; p = 0.379), even though the probiotic group had a numerically lower average number of UTI episodes compared to the placebo group. The mean number of UTIs was considered for five patients in the probiotic and sixteen patients in the placebo group. Patients who did not experience recurrence were not included in this calculation.

3.2. Urinary Nerve Growth Factor (NGF) and Serum Macrophage Colony-Stimulating Factor (M-CSF Levels) Levels

3.2.1. Change in Urinary Nerve Growth Factor (NGF)

The mean urinary NGF levels decreased from 38.75 pg/mL at baseline to 20.39 pg/mL at 24 weeks in the probiotic-treated group and from 36.43 pg/mL at baseline to 18.72 pg/mL at 24 weeks in the placebo group (per protocol analysis). The changes in both groups were statistically significant at the end of treatment as compared to the baseline. However, there was no significant difference between the probiotic and placebo groups (0.649; 95% CI: −5.29 to 6.59; p = 0.827).

Similar results were obtained for mITT analysis.

3.2.2. Change in Serum Macrophage Colony-Stimulating Factor (M-CSF Levels)

The mean serum M-CSF levels decreased from 36.13 pg/mL at baseline to 32.45 pg/mL at 24 weeks in the probiotic group and from 32.24 pg/mL to 26.04 pg/mL in the placebo group (per protocol analysis). The change from baseline to 24-weeks follow-up was significant in both groups. There was no significant difference between the groups in the per-protocol analysis (95% CI: −5.52 to 0.49; p = 0.098).

The results were statistically significant for the mITT analysis (mean diff: −5.52; 95% CI: −3.55 to −1.50), though the numerical value of difference remained the same.

3.3. Adverse Events

No adverse events were reported in either of the groups.

4. Discussion

In the present study, the administration of a multi-strain probiotic formulation as an adjunct treatment, along with standard antibiotic therapy, resulted in a significant reduction in UTI recurrence in the probiotic group compared with the placebo group. This reduction suggests that combining probiotics with antibiotics may create a synergistic effect, enhancing overall treatment efficacy. For individuals prone to recurrent infections, especially women, adjunctive probiotic therapy could offer a preventative strategy that supports antibiotic function while reducing reliance on repeated antibiotic courses. Such an approach may be particularly advantageous for managing complex, recurrent infections in a manner that lessens the risk of antibiotic resistance. Our findings align with some studies on other probiotic formulations [13,20]. However, other studies have reported no efficacy [15,21].

Given the mixed results on the role of probiotics in managing UTIs [22,23], it is crucial to recognize the variability among probiotic strains, and it is therefore essential to establish the clinical efficacy of probiotic formulations recommended for patients with UTIs. Each strain can exhibit unique properties, from antimicrobial activity and immune modulation to biofilm inhibition and mucosal adherence, contributing to variable clinical outcomes. Differences in study designs, population characteristics, and dosage frequencies further contribute to inconsistencies in findings, suggesting that a “one-size-fits-all” approach is inadequate for probiotic therapy in UTI management. As such, establishing the clinical efficacy of specific probiotic strains or formulations for UTI management remains essential. Precision approaches, perhaps guided by baseline microbiota profiles, may help tailor probiotic interventions to individual needs and enhance efficacy.

The mechanisms underlying the beneficial effects of probiotics on UTI prevention include antipathogenic activity against the invading pathogens involved in the etiology of UTI, modulation of the urogenital microbiota, and the reinforcement of the mucosal barrier, which helps impede the establishment of uropathogenic infections [24,25]. These mechanisms operate synergistically, where antimicrobial properties act immediately against pathogens, while long-term modulation of the microbiome and enhancement of the mucosal barrier contribute to sustained infection prevention. Additionally, probiotics disrupt biofilm formation—a critical factor in the persistence and recurrence of UTIs. Uropathogens like E. coli are known to form biofilms on urinary tract epithelial cells, providing them with a protective shield against immune defenses and antibiotics. Probiotics, especially those producing organic acids and hydrogen peroxide, can inhibit biofilm formation and help break down existing biofilms, thus reducing bacterial colonization. The probiotic strains in the formulation were selected based on their antipathogenic activity against E. coli (in vitro studies) and anti-inflammatory properties. These specific properties make the strains suitable for counteracting both pathogen invasion and the inflammatory responses that accompany recurrent UTIs. By including strains with both antimicrobial and anti-inflammatory characteristics, this multi-strain formulation aims to address not only the immediate bacterial challenge but also the inflammatory cascades associated with infection recurrence, which can disrupt mucosal integrity and predispose individuals to new infections. Probiotic strains of Lactobacillus offer potential preventive effects against recurrent urinary tract infections (rUTIs) by providing several advantages [24], which include restoring equilibrium to the vaginal flora following antimicrobial treatment for an initial UTI, assisting in the maintenance of a typical vaginal pH of <4.5 through the production of lactic acid, generating the microbicidal compound H2O2, modulating the host’s immune system, competitively excluding uropathogens, and producing antibacterial substances, such as bacteriocins [26]. These benefits create an environment hostile to uropathogens while favoring the growth of beneficial bacteria, thus lowering the risk of new infections. Through competitive exclusion, Lactobacillus strains can prevent uropathogens from adhering to epithelial surfaces, a critical initial step in the infection process. Furthermore, Lactobacilli produce bacteriocins—proteinaceous toxins that target other bacteria—which further hinder the establishment of harmful microbes. Enhancing the health of gut or vaginal flora can exert a significant influence on the urinary tract, as Escherichia coli (E. coli), the primary pathogenic agent in urinary tract infections (UTIs), typically moves from the rectum to the vagina and subsequently ascends up the sterile urinary tract through a process known as ascending infection. As Lactobacillus species predominantly govern the vaginal microbiota’s well-being, it has been suggested that administration of exogenous probiotics containing Lactobacilli has lowered the risk of recurrent UTIs and BV. Particularly for women with a history of recurrent and complicated UTIs or those undergoing prolonged antibiotic treatment, Lactobacilli strains prove to be especially beneficial. Additionally, probiotics do not contribute to antibiotic resistance and may confer additional health advantages by promoting the re-establishment of lactobacilli in the vaginal environment. The multi-strain probiotic formulation used in this study, consisting of lactobacillus and bifidobacterium sps, has previously been found to be effective in the treatment of Bacterial Vaginosis [27], and, hence, in the present study, efficacy in preventing the recurrence of UTI was evaluated. Additionally, it has also been found to be efficacious in the management of PCOS and its symptoms [28]. Bifidobacterium species in particular, known for their immunomodulatory and anti-inflammatory properties, may play a supportive role in reducing systemic inflammation, which has implications for both UTI and PCOS management. Such beneficial bacteria may positively influence overall immune function, potentially providing a holistic benefit for individuals prone to recurrent infections and inflammatory conditions.

It has been suggested that both serum macrophage colony-stimulating factor and urinary nerve growth factor hold promise as potential predictive markers for recurrent urinary tract infections [29]. These biomarkers could offer a valuable, non-invasive approach to monitoring patients at high risk for UTI recurrence, as they reflect underlying inflammatory and nerve-related changes associated with frequent infections. Measuring these markers in clinical settings might help identify individuals at increased risk, allowing for early intervention and tailored prevention strategies. At the conclusion of the 24-week treatment period, a notable reduction in the biomarkers was observed in both the probiotic and placebo groups when compared to their respective baseline values (intergroup comparison). However, when examining the levels of urinary nerve growth factor (NGF) and serum macrophage colony-stimulating factor (M-CSF) between the groups (intragroup comparison), no significant differences were found between the probiotic and placebo groups. This suggests that standard antibiotic treatment (during a UTI episode) per se may have led to a concurrent decrease in biomarkers and that additional multi-strain probiotic therapy did not show a discernible impact.

The present study indicated that the recurrence of urinary tract infections was significantly less in the multi-strain probiotic-treated group as compared to the placebo group. Although urinary biomarkers showed a trend toward improvement in individual groups, statistical significance was not achieved between the groups. The change in serum macrophage colony-stimulating factor showed a numerically small difference but achieved a statistical significance in the ITT analysis between the groups. This finding suggests that, while probiotics may contribute to reducing infection recurrence, their effect on specific inflammatory markers may require longer intervention periods or higher dosages to demonstrate a clear impact. Future studies might examine whether optimizing dosage or treatment duration could enhance these outcomes.

Despite the encouraging results, several limitations should be considered when interpreting our findings. The study duration, sample size, and participant demographics may influence the generalizability of our results. The relatively short study duration may limit our understanding of the long-term effects and sustainability of probiotic treatment for UTI prevention. Additionally, the relatively small sample size and the specific demographics of the participants—such as age, health status, and baseline UTI risk factors—may impact the generalizability of our results. Expanding future research to include larger, more diverse populations with varied baseline microbiota compositions and extending follow-up periods would provide a more comprehensive understanding of probiotic efficacy.

5. Conclusions

Our clinical trial contributes valuable evidence supporting the potential of probiotics in preventing recurrent UTIs among women. This study highlights probiotics as a complementary approach to antibiotics, especially relevant given the issue of antibiotic resistance. By showing reduced recurrence rates, probiotics present an alternative for women experiencing frequent UTIs who are at greater risk of resistance due to repeated antibiotic use. These findings open avenues for future research exploring optimal probiotic formulations, duration of treatment, and identifying specific subgroups that may benefit the most. Further studies could refine which probiotic strains are most effective for targeting pathogens like E. coli, considering variations across age groups, hormonal changes, and health conditions. This personalized approach could enhance prevention strategies, especially for higher-risk groups like postmenopausal women or those with immune-compromising conditions. Incorporating probiotics into UTI prevention strategies holds promise for improving women’s urogenital health and reducing the burden of recurrent UTIs in the broader population. By supporting microbial balance, probiotics could reduce antibiotic use and associated healthcare costs, aligning with a preventive healthcare model. Additionally, probiotics’ general safety and potential to limit antibiotic side effects make them appealing as a sustainable UTI management option, potentially influencing clinical practices and guidelines.