Efficacy of probiotics for oral candidiasis management: a systematic review

Abstract

Background

Oral candidiasis is a common opportunistic fungal infection caused by the genus Candida that primarily affects immunocompromised individuals. However, the clinical application of antifungal agents still faces frequent side effects and antifungal resistance, highlighting the urgent need for alternative therapeutic options. This systematic review aimed to synthesize RCT evidence up to February 2025, comprehensively comparing clinical outcomes across various probiotic regimens, in order to assess the efficacy of probiotics for oral candidiasis.

Methods

A literature search was conducted to identify randomized clinical trials (RCTs) comparing probiotic regimens (multi-strain combinations or strain-specific interventions) with control groups. Thirteen RCTs were analyzed, using a classical frequentist meta-analysis model. Outcomes focused on the odds ratio (OR) of oral candidiasis (defined as CFU/mL > 10³ or 10⁴) and heterogeneity across studies. The analysis integrated evidence up to February 2025 to comprehensively assess clinical outcomes.

Results

The meta—analytic OR was 0.38 (95% confidence interval (95%CI): 0.22, 0.68), indicating a beneficial effect of treatment; the I²index was 60.3%. Focusing on participants diagnosed with oral candidiasis or related diseases, the OR was 0.40 (95% CI, 0.23, 0.70), with an I²index of 18.2%.

Conclusion

The treatment effect in the susceptible populations appeared to have lower heterogeneity and more stable outcomes, indicating that the application of probiotics is beneficial for oral candidiasis, and the effects vary according to the population characteristics and sample size. Owing to the small sample size and high-risk studies, the results should be interpreted with caution.

Introduction

Oral candidiasis is a common opportunistic fungal infection caused by the genus Candida that primarily affects immunocompromised individuals. Globally, approximately 5% to 7% of immunocompromised populations are impacted [1], including patients undergoing chemotherapy, HIV/AIDS patients, and elderly individuals wearing dentures for prolonged periods [2–4]. Candida species are ubiquitous in the human microbiota and colonize areas such as the skin, oral cavity, gastrointestinal tract [5, 6], urogenital tract, and respiratory tract. Under normal circumstances, Candida maintains balanced coexistence with the host. However, when the host's immune system is compromised, antibiotics are used, or dentures are worn for extended periods, Candida may transform into a pathogenic form, leading to infection.

The main pathogen causing oral candidiasis is Candida albicans, although other species, such as Candida parapsilosis and Candida tropicalis, may also be involved [7]. Clinically, the disease presents with various phenotypes including pseudomembranous, erythematous, hyperplastic forms, candidal angular cheilitis (perlèche), denture-associated stomatitis, and median rhomboid glossitis. Hyperplastic oral candidiasis is known to be a precursor to oral cancer (Oral Potentially Malignant Disorders, OPMD) with a higher risk of malignant transformation into oral squamous cell carcinoma (OSCC) [8], necessitating early treatment and timely intervention.

Despite advances in antifungal therapies, the emergence of resistance to conventional antifungal agents has become a pressing challenge [9]. This escalating resistance not only restricts therapeutic options for patients but also heightens the risks of recurrent infections and mortality, underscoring the urgent need to explore alternative therapeutic strategies [10–12]

In recent years, probiotics have gained significant attention as potential therapeutic agents. Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits to the host [13]. Their mechanism of improving oral health parallels the findings from gastrointestinal research, as the oral cavity is one of the five major microbial reservoirs in the body. Emerging evidence supports probiotic mechanisms of action; certain antimicrobial effects are attributed to bacteriocins, organic acids, hydrogen peroxide, and other metabolites produced by probiotics [14]. For example, Lactobacillus species suppress pathogen growth by modulating the microenvironment (e.g., pH or redox status) and secreting organic acids, such as lactic and acetic acids, which reduce fungal ATP synthesis and inhibit proliferation [15]. Additionally, Lactobacillus demonstrates potent inhibitory effects on biofilm formation and filamentation of Candida albicans, Candida tropicalis and Candida parapsilosis, specially L. acidophilus, conversely, had little effect on C. albicans and C. tropicalis but was more effective on inhibiting C. parapsilosis biofilms [16].

Current research on probiotic efficacy primarily focuses on in vitro and animal studies, with limited randomized controlled trials (RCTs). However, RCTs represent high-level proof in evidence-based medicine (EBM), necessitating the inclusion and synthesis of all current RCT data in a meta-analysis to establish robust guidelines for clinical application.

This systematic review and meta-analysis aimed to synthesize RCT evidence up to February 2025, comprehensively comparing clinical outcomes (e.g., cure rate, disease prevalence, and Candida CFU/ml) across various probiotic regimens, such as multi-strain combinations versus single-strain interventions. By incorporating high-quality RCTs, targeting specific susceptible populations, and analyzing large-sample studies, this work will clarify the effectiveness of probiotics across diverse groups. Distinct from prior reviews limited to pre-2019 data, this study integrates new research advancements in probiotics and standardized evaluations of antifungal-probiotic synergies, providing evidence to inform clinical practice guidelines and future research directions.

Materials and methods

Search strategy

The systematic review protocol was executed following PRISMA 2020 guidelines. Electronic database searches spanned Ovid EMBASE, PubMed, Web of Science (limited to clinical trials), and the Cochrane database, with date parameters set from database inception to February 10, 2025. To ensure exhaustive coverage, supplementary searches included scrutiny of clinical trial registries (ClinicalTrials.gov, ICTRP), and reference lists of relevant systematic reviews. The search strategy for PubMed and Web of Science employed the following syntax:

Pubmed:(((((((((((("Candidiasis, Oral"[Mesh]) OR (Candidiases, Oral[Title/Abstract])) OR (Oral Candidiases[Title/Abstract])) OR (Oral Candidiasis[Title/Abstract])) OR (Moniliasis, Oral[Title/Abstract])) OR (Moniliases, Oral[Title/Abstract])) OR (Oral Moniliases[Title/Abstract])) OR (Oral Moniliasis[Title/Abstract])) OR (Thrush[Title/Abstract])) OR (candidosis[Title/Abstract])) OR (oral Candida spp.[Title/Abstract])) OR (yeast infection[Title/Abstract])) AND ((("probiotics"[MeSH] OR"probiotic*"[tiab] OR"Lactobacillus"[tiab] OR"Bifidobacterium"[tiab] OR"Saccharomyces"[tiab] OR"microbiota therap*"[tiab] OR"live biotherapeutics"[tiab])) OR (Bacillus[Title/Abstract])).

Web of Science: ((((((((((TS = (Candidiasis, Oral)) OR TS = (Candidiases, Oral)) OR TS = (Oral Candidiases)) OR TS = (Oral Candidiasis)) OR TS = (Thrush)) OR TS = (Moniliasis, Oral)) OR TS = (Oral Moniliases)) OR TS = (Oral Moniliasis)) OR TS = (candidosis)) OR TS = (oral Candida spp.)) OR TS = (yeast infection) AND ((((((((TS = (probiotics)) OR TS = (probiotic*)) OR TS = (Lactobacillus)) OR TS = (Bifidobacterium)) OR TS = (Saccharomyces)) OR TS = (microbiota therap*)) OR TS = (live biotherapeutics)) OR TS = (Bacillus)) NOT (SILOID =  = ("PPRN")).

Detailed search strategies for EMBASE and the Cochrane Library are presented in Table 1 and Table 2.

Table 1.

Embase Search Strategy

Table 2.

Cochrane Library Search Strategy

Eligibility criteria

Two authors independently screened the titles and abstracts of the identified records according to the inclusion/exclusion criteria.

Inclusion criteria:

1. Randomized controlled trials (RCTs) comparing probiotics with antifungal drugs, placebo, no treatment, or alternatives;

2. Patients of any age, sex, ethnicity, or health status;

3. Studies evaluating probiotics administered in any form (e.g., lozenges, mouthwash, yogurt) with clearly described dosage, strain composition, and treatment duration;

4. Quantifiable microbiological outcomes (e.g., Candida CFU/mL in saliva/palatal samples) or prevalence of yeast infections;

5. Full-text peer-reviewed articles published in English;

Exclusion criteria:

1. Non-interventional studies (e.g., reviews, case reports, cohort studies), non-human research, or unpublished data (e.g., conference abstracts, patents);

2. Trials with a total sample size of fewer than 10 participants;

3. Studies lacking quantifiable outcome measures or incomplete data for meta-analysis;

4. Intestinal, vulvovaginal, or systemic candidiasis.

Data extraction

For each article that met the inclusion criteria, data were extracted into a standardized table format containing the following elements: author(s), publication year, country of origin, population characteristics, sample size, intervention details, comparison groups, follow-up period, and measured outcomes.

Risk of bias of the included studies

Two reviewers independently evaluated the methodological quality of the included studies using the Cochrane Risk of Bias Tool (RoB 2.0) as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. The assessment was conducted using Review Manager software (version 5.3; RevMan 5.3). For each study, reviewers assigned risk of bias judgments (low risk, high risk, or unclear) across seven predefined domains:

1. Random sequence generation,

2. Allocation concealment,

3. Blinding of participants and personnel,

4. Blinding of outcome assessment,

5. Incomplete outcome data,

6. Selective reporting,

7. Other potential sources of bias.

To ensure reliability, both reviewers performed assessments independently. Any discrepancies in judgments were resolved through discussion, and unresolved disagreements were adjudicated by a third investigator to reach consensus.

Outcome assessment

For seven RCTs reporting categorical outcomes (detection/colonization/prevalence rates of Candida spp.) in 2 × 2 contingency tables, we directly calculated odds ratios (ORs) with corresponding 95% confidence intervals (CI). For three trials dichotomizing continuous microbiological measures using predefined thresholds (10³ or 10⁴ CFU/mL), we similarly derived ORs and CIs through contingency table analysis based on these clinically validated cutoffs. For three additional RCTs reporting continuous outcome measures, we initially calculated standardized mean differences (SMDs) between probiotic and control groups, followed by conversion to OR metrics with 95% CI using the Hasselblad and Hedges transformation method to ensure comparability across studies.

Statistical analysis

The meta-analysis was executed using R statistical software (version 4.4.2; R Foundation) [17] with the meta package. A random-effects model or a fixed-effect model was implemented to synthesize data from included randomized controlled trials (RCTs), generating pooled odds ratios (ORs) with 95% confidence intervals (CIs) as effect size measures for evaluating probiotic efficacy against oral candidiasis. When I² < 50% accompanied by a non-significant Q-test (p > 0.05) are considered to have acceptable heterogeneity according to Cochrane Collaboration thresholds, we choose a fixed-effect model. Conversely, we consider the studies high heterogeneity, therefore, it is better to use random-effects model.

To investigate potential sources of heterogeneity, sensitivity analyses were conducted through sequential exclusion of individual studies using the leave-one-out method. Stratified subgroup analyses were systematically performed across predefined covariates, based on population characteristics and sample size. Publication bias was evaluated through both visual inspection of funnel plot symmetry and formal statistical testing via Egger’s weighted regression (α = 0.05).

Results

Study selection

The literature search yielded 2,541 initial records. After removing 225 duplicates, 2,316 articles were subjected to title/abstract screening. Of these, 2,293 were excluded because they were irrelevant to the research question. Full-text assessment was performed on 23 potentially eligible articles, with subsequent exclusions for the following reasons: Five studies excluded for incomplete outcome data; One non-English publication; Three articles with non-RCT designs; One study reporting irrelevant outcomes. Thirteen studies met all the eligibility criteria and were included in the quantitative synthesis (meta-analysis).

Figure 1 illustrates the selection process, according to the PRISMA statement 2020.

Fig. 1.

PRISMA flow diagram

Characteristics of the included studies

Table 3 summarizes the key characteristics of the included studies, presenting the following variables: first author, publication year, country, population demographics, sample size, intervention details, control group parameters, follow-up duration, and primary outcome measures.

Table 3.

Characteristics of the included studies

The analysis encompassed 13 randomized controlled trials (RCTs) published between 2007 and 2024, with a cumulative sample size of 898 participants. Individual study sample sizes ranged from 13 to 192 subjects. Six studies enrolled participants with larger sample sizes (≥ 60 participants), whereas the remaining trials maintained smaller sample sizes (range: 13–59).”

Seven investigations [18, 20, 21, 23, 25, 29, 30] recruited asymptomatic individuals without clinical evidence of denture stomatitis or candidiasis; Three trials [19, 26, 27] specifically enrolled patients with confirmed oral candidiasis diagnoses; The remaining studies focused on special populations, including oral lichen carious teeth [22], planus patients [24] and participants with HIV-positive individuals [28].

The patients varies from 9 countries: India, China, Egypt, Finland, Brazil, Denmark, Sweden, Chile, Iran.

The systematic analysis identified 12 distinct probiotic interventions across the included trials, with two studies [21, 24] utilizing identical probiotic formulations. Strain composition analysis revealed that 75% (9/12) of interventions employed multi-species combinations, while the remaining 25% (3/12) adopted single-strain protocols, specifically Lactobacillus rhamnosus SP1 [26], Streptococcus salivarius K12 [27], Lactobacillus acidophilus NCFM in experimental group 1,and L. rhamnosus Lr-32 in experimental group 2 [23].

In dosage regimens, colony-forming units (CFU) ranged from 5 × 10⁵ to 1 × 10¹⁰ CFU/mL. Administration frequencies varied across trials: single daily dosing, twice daily, and three times daily, with 23.1% (3/13) of studies failing to report temporal administration details relative to meals or oral hygiene activities.

The duration of the follow-up ranged from a minimum of 1 week to a maximum of 24 weeks.

The reported outcome measures were different among studies, varying from continuous variable (the means of CFU/mL) with/without different thresholds of Candida spp. counts (10³or 10⁴) to dichotomous variable (e.g. detection/colonization/prevalence rates of Candida spp.)

Evaluation of the risk of bias for RCTs

The risk of bias assessment demonstrated variable methodological quality across included studies. Regarding randomization procedures, 53.8% of the RCTs (7/13) adequately described random sequence generation, while eight studies (61.5%) reported allocation concealment in detail. Blinding implementation was noted in 69.2% of studies (9/13) for participants and personnel, with ten studies maintaining outcome assessor blinding; however, one trial [29] was rated high risk due to unblinded outcome assessment. Attrition bias analysis revealed seven studies with low risk, contrasted by three trials [18, 24, 28] exhibiting high risk attributable to substantial participant dropout (> 25% attrition rate). Selective reporting bias was uniformly low across all articles. Additionally, one study [25] was classified as high risk in other biases due to incomplete baseline characteristic documentation, which likely compromised outcome validity.

The results of the risk of bias evaluation are reported in Fig. 2.

Fig. 2.

Risk of bias summary and graph

Meta-analysis results

The results of the Classical frequentist meta-analysis conducted on the 13 evaluated studies are reported in the Fig. 3.

Fig. 3.

Forest plot

The pooled analysis demonstrated a statistically significant reduction in oral candidiasis (OC) risk among participants receiving probiotics compared to controls, with an odds ratio (OR) of 0.38 (95% CI: 0.22–0.68). This corresponds to an estimated 60% lower odds of OC incidence in the probiotics group. Substantial heterogeneity was observed across trials, as evidenced by an I² value of 60.3% and a Cochran’s Q test p-value of 0.0013, necessitating the application of a random-effects model.

Given the substantial between-study heterogeneity (I² = 60.3%), sensitivity analyses were performed by iteratively excluding individual trials. The results demonstrated that the heterogeneity originated predominantly from the trial conducted by Ishikawa et al. (2015). Notably, exclusion of this trial reduced the I² statistic from 60.3% to 38.8% (p = 0.0681 for residual heterogeneity). This outcome may be attributable to the trial's notably small sample size (n = 55), which may have inflated effect estimates due to overrepresentation of positive outcomes in limited populations. Specifically, Ishikawa et al. reported a 83.3% candidiasis reduction rate in the probiotic group compared to 8% in controls, diverging markedly from the pooled estimate of 62% reduction across other studies. (Fig. 4).

Fig. 4.

Sensitivity analyses

When subgroup analyses were performed based on trial sample sizes and population characteristics, the effect sizes (odds ratios and 95% confidence intervals) demonstrated distinct patterns. In the first stratification, the large sample size subgroup (n ≥ 60) showed an OR of 0.51 (95% CI: 0.37–0.71) with negligible heterogeneity (I² = 0%, p > 0.05), indicating consistent treatment effects across studies in this category. Conversely, the small sample size subgroup (n < 100) exhibited a more pronounced effect size (OR = 0.23, 95% CI: 0.06–0.92), suggesting potentially stronger efficacy in oral candidiasis (OC) treatment outcomes. However, this subgroup displayed substantial heterogeneity (I² = 75.9%, p = 0.0001), implying significant variability in study outcomes that may be attributed to limitations inherent to underpowered studies. (Fig. 5, Fig. 6).

Fig. 5.

Large sample size

Fig. 6.

Small sample size

In the secondary subgroup analysis, the studies were stratified according to population characteristics into two distinct cohorts: Group A comprised participants diagnosed with oral candidiasis (OC) or related diseases, while Group B consisted of individuals without any clinically relevant orofacial pathologies.

Group A showed an OR of 0.40 (95% CI: 0.23–0.70) with mild heterogeneity (I² = 18.2%, p > 0.05), indicating consistent treatment effects across studies in this category. Conversely, Group B exhibited a more pronounced effect size (OR = 0.36, 95% CI: 0.12–1.08), implying mightly the distribution of the sample size or the participants who suffer from systematic chronic diseases (e.g., cardiovascular diseases or diabetes) but unnoticed by the investigators could affect the prevalence of oral candidiasis.

In subgroup analyses, Group A indicated a statistically risk reduction (OR 0.40, 95%CrI 0.23–0.70) with minimal between-study heterogeneity (I² = 18.2%, p > 0.05), suggesting consistent therapeutic effects across studies in this stratum. In contrast, Group B indicated a more substantial effect magnitude (OR = 0.36, 95% CI: 0.12–1.08), suggesting that this paradoxical association may be attributable to either imbalanced sample size distribution or undetected confounding from preexisting systemic comorbidities (e.g., cardiovascular disorders or diabetes mellitus) that were not adequately controlled for in the analytical model, potentially influencing oral candidiasis pathogenesis. (Fig. 7, Fig. 8).

Fig. 7.

Group A: participants diagnosed with oral candidiasis or related diseases

Fig. 8.

Group B: individuals without any clinically relevant orofacial pathologies

A summary of the meta-analyses results is presented in Table 4.

Table 4.

Summary of the results from the meta-analyses

Our subgroup analyses revealed heterogeneity across studies, indicating the imperative for future research to prioritize three key methodological enhancements: expanded sample sizes powered to detect clinically meaningful effects, standardized inclusion/exclusion criteria to minimize confounding, and rigorously designed randomized controlled trials (RCTs) employing.

Visual assessment of funnel plot symmetry did not demonstrate conclusive evidence of publication bias. However, Egger's regression test revealed statistically asymmetry (p = 0.044), suggesting potential publication bias may exist in the included studies. It will be discussed in the following section.

From the inspection of the funnel plot, no evidence of publication bias arose (Fig. 9).

Fig. 9.

Funnel plot of publication bias

Discussion

Currently, antifungal drugs are considered first-line treatment options with significant efficacy. However, clinical applications still face several challenges such as frequent side effects and antifungal resistance [31]. Consequently, the development of novel prevention and treatment strategies is becoming increasingly important. The current controversy centers on the efficacy of probiotics as an adjunctive or preventive measure for oral diseases [32–35]. In vitro studies have shown that different probiotic strains exhibit beneficial effects on oral pathogens. In vivo studies have also suggested that probiotics may play a role in the prevention or treatment of periodontal disease and dental caries. Certain strains (e.g., Lactobacillus reuteri and Saccharomyces boulardii) exhibit antifungal potential by modulating mucosal immunity and competitively inhibiting Candida adhesion [36, 37]. However, some trials have reported contradictory results [38, 39]. A study reported that there were no significant changes in oral Candida counts among seven elderly denture wearers after consuming probiotic beverages for four weeks [40]. Similarly another study demonstrated no significant benefit of probiotic or prebiotic supplements in immunocompromised patients [41]. Additionally, A randomized controlled trial (RCT) conducted by Miyazima also demonstrated unclear preventive effects of L. acidophilus NCFM and L. rhamnosus Lr-32 in healthy denture-wearing patients. Collectively, current positive findings have been predominantly observed in in vitro experiments and animal models, necessitating further validation through large-scale clinical trials with robust sample sizes [36, 42, 43].

Currently, probiotic interventions for oral candidiasis (OC) primarily focus on single-strain formulations (e.g., Lactobacillus reuteri DSM 17938 or Lactobacillus johnsonii MT4) [42], postbiotic therapies (e.g., Iturin A) [44], and multi-strain probiotic regimens (e.g., Lactobacillus acidophilus + Bifidobacterium lactis), all of which demonstrate therapeutic effects in suppressing fungal colonization and biofilm formation [45, 46].

Furthermore, previous meta-analyses have predominantly focused on healthy populations or individuals without clinical signs of oral candidiasis, leaving the efficacy of probiotics in immunocompromised/immunodeficient populations unclear. Early studies were also limited by the scarcity of randomized controlled trials (RCTs), resulting in underpowered meta-analyses (RCT count < 10) [47] and unstable effect estimates (confidence intervals crossing 1). To address these limitations, this systematic review incorporated newly published RCTs (2019–2024) and employed a random-effects model to quantify pooled efficacy estimates (risk ratio [RR] and 95% confidence intervention[CI]) of probiotics in experimental versus control groups, with results stratified by host susceptibility (e.g., immunocompromised patients).

In our research, the study conducted by Hu [27] et al., suggested that probiotic-antifungal combination therapy achieved clinically meaningful reductions in treatment duration for oral candidiasis (OR = 0.12, CI:0.02–0.64) with robust statistical significance (p = 0.008). In the preceding section, we conducted a detailed subgroup analysis of the potential effects of various covariates on the outcome effect size (OR) and their underlying mechanisms.

In addition, while visual assessment of funnel plot symmetry revealed no conclusive asymmetry, Egger's regression test indicated borderline statistical significance (P = 0.044), suggesting potential publication bias [48]. Subsequent trim-and-fill [49, 50] adjustment identified no imputed studies (k = 0), preserving the original pooled effect size. However, the limited sensitivity of this method in small meta-analyses warrants further caution. Complementary fail-safe N analysis [51–53] demonstrated modest robustness (N = 20), falling substantially below Rosenthal's conservative threshold (N < sub > fs </sub >  > 5 K + 10 = 85), indicating susceptibility to unpublished null-effect studies. Meanwhile, Sensitivity analyses demonstrated a significant reduction in heterogeneity (I² decreased from 60.3% to 38.8%) and rendered Egger's test results non- (p = 0.16) following the exclusion of Ishikawa [20] et al. (2015).

All above the results likely stem from three interrelated factors: type I error inflation due to the limited number of included studies (k = 15) and insufficient statistical power; heterogeneity-driven distortion evidenced by substantial between-study variance (τ² = 0.76, I² = 60.3%); and small-study effects bias, where trials with limited sample sizes and extreme effect estimates (e.g., Ishikawa [20] et al. 2015: OR = 0.02) disproportionately influenced the pooled results.

Collectively, these findings emphasize the necessity for large-scale randomized controlled trials that employ standardized protocols. Future research should prioritize incorporating high-quality studies, particularly those reporting non-significant outcomes, to mitigate the risk of current conclusions being compromised by unpublished data.

Although the short-term efficacy of probiotics in OC (oral candidiasis) has been demonstrated, their safety profile in immunocompromised or clinically vulnerable populations remains uncertain. A three-arm randomized double-blind placebo-controlled trial conducted by Chen [54] et al. demonstrated no significant differences in infant growth parameters between probiotic and placebo groups, suggesting apparent biological safety. However, emerging evidence from clinical case reports challenges this hypothesis. Notably, a case report documented a male patient with severe congestive heart failure who developed Lactobacillus bacteremia following probiotic administration [55]. Concurrently, genomic and epidemiological investigations in ICU populations have revealed that probiotic strains not only directly induce bacteremia, but also undergo adaptive evolution in hospitalized patients [56]. Furthermore, recent research has identified probiotic-associated mobile genetic elements (MGEs) capable of mediating the horizontal transfer of antimicrobial resistance genes to the commensal gut microbiota [57, 58].

By means of the above—mentioned evidence, it will be more conducive to future clinical drug use and network meta-analysis. Network meta-analysis (NMA), which is recognized for its ability to clarify the comparative efficacy of specific probiotic strains (either single-strain or combined-formulation) in clinical scenarios, can serve as a reliable guide for clinical treatment selection. There is an urgent need for rigorously designed randomized controlled trials (RCTs) to formulate standardized protocols for strain selection, dosage determination, and treatment duration to achieve precise screening and efficient administration methods for probiotic therapy. To delineate the risk–benefit equilibrium of probiotic interventions, prolonged follow-up studies are critically needed to evaluate their long-term therapeutic efficacy and safety profiles. Such longitudinal assessments will not only elucidate the efficient administration methods of microbes, but also enable the refinement of protective strategies for vulnerable populations, particularly immunocompromised individuals predisposed to microbial dysbiosis and opportunistic infections. Establishing standardized, evidence-based guidelines through these investigations and achieving customizable and personalized probiotic therapeutic regimens are paramount for optimizing clinical outcomes and ensuring the judicious application of probiotics in high-risk populations.

Our study has several notable limitations. Primarily, the current evidence base is constrained by the limited availability of high-quality randomized controlled trials (RCTs), which precludes robust network meta-analysis (NMA) because of insufficient data to establish a connected comparison network. This discontinuity fundamentally violates the transitivity assumption required for NMA [59], thereby limiting our ability to hierarchically rank interventions or quantify relative effect sizes. Secondly, some of the included studies exhibited methodological limitations, including a high risk of bias and/or inadequate sample sizes. These issues contributed to substantial heterogeneity across trials and likely inflated the magnitude of treatment effect estimates. Finally, although we searched electronic databases including Ovid EMBASE, PubMed, Web of Science (limited to clinical trials), and the Cochrane database, and reviewed clinical trial registries (ClinicalTrials.gov, ICTRP) along with reference lists of relevant systematic reviews, we did not search other important databases such as Scopus or search engines like Google Scholar, which might compromise the comprehensiveness of our article.

Conclusions

In conclusion, our meta-analysis is a comparatively comprehensive (included 13RCTs) systematic review in the efficacy of probiotics for oral candidiasis management among studies. We have confidence to declare that the probiotics treatment exert a positive effect on reducing oral Candida spp. counts.

Abbreviations

OR

Odds Ratio

OPMD

Oral Potentially Malignant Disorders

OSCC

Oral Squamous Cell Carcinoma

EBM

Evidence-based Medicine

RCT

Randomized Clinical Trial

RR

Risk Ratio

MGEs

Mobile Genetic Elements

NMA

Network Meta-analysis

SE

Standard Error

95% CI

95% Confidence Interval

Authors’ contributions

Conceptualization: P.L.; literature search, data extraction: P.L., X.Y.; quality evaluation, data curation:C.C., P.L.; statistical analysis: P.L., Z.Z; writing—original draft preparation: P.L., C.C., X.Y.; writing—review and editing: Y.F., X.L.; supervision of methods, X.L., Z.Z.; project administration, Y.F.;corresponding author: Y.F.,X.L..

Funding

This work was supported by the Special Fund of Jiangsu Provincial Key Research and Development Project (Social Development) (BE2021723), National Nature Science Foundation of China (Grant No. 82470979), the Jiangsu Province Capability Improvement Project through Science, Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit (YJXYYJSDW4), and the Jiangsu Provincial Medical Innovation Center (CXZX202227).

Data availability

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.