Clinical efficacy of Lactobacillus plantarum and Lactobacillus brevis as adjuncts to professional mechanical plaque removal in periodontitis: a systematic review

Abstract

Background

Periodontitis is a prevalent chronic inflammatory disease marked by progressive periodontal tissue destruction. It is classified according to the 2017 AAP/EFP staging and grading framework and managed in accordance with the EFP S3-level guideline. Professional mechanical plaque removal (PMPR) remains the cornerstone of non-surgical therapy. However, its limited effectiveness in deep periodontal pockets has prompted interest in adjunctive probiotic approaches. These include Lactobacillus plantarum and Lactobacillus brevis, which exhibit antimicrobial and immunomodulatory properties.

Methods

A PRISMA 2020–compliant systematic search of five databases identified randomized controlled trials evaluating L. plantarum and L. brevis as adjuncts to PMPR in periodontitis. The findings were synthesized descriptively.

Results

Adjunctive subgingival delivery of a probiotic gel containing Lactobacillus plantarum and Lactobacillus brevis was associated with significant improvements in PPD, CAL, and IL-10 compared with PMPR alone. In contrast, systemic or combined application showed inconsistent or nonsignificant effects. Clinical benefits were more evident in stage I–II periodontitis, whereas evidence in stage III–IV disease remained inconclusive.

Discussion

Three randomized controlled trials were included. While clinical parameters improved following PMPR in all groups, additional benefits from probiotics were observed primarily in early-stage periodontitis with subgingival delivery. Findings in advanced-stage disease were inconsistent and often not statistically significant, suggesting that treatment response may depend on disease stage and delivery method.

Conclusion

Adjunctive subgingival application of Lactobacillus plantarum and Lactobacillus brevis may offer short-term clinical benefits, particularly in stage I–II periodontitis. However, evidence in stage III–IV remains inconsistent and often not statistically significant. Given the limited number of heterogeneous trials, further well-designed studies are needed to establish their clinical relevance.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-026-08032-z.

Introduction

The gingiva, cementum, alveolar bone, and periodontal ligament are among the supporting tissues of the teeth that are impacted by the common inflammatory ailment known as periodontal disease. It is primarily initiated by the accumulation of pathogenic microbial biofilms and modulated by the host’s inflammatory response. Periodontitis is a major global challenge in oral health management due to its progressive nature, which can lead to irreversible tissue damage and ultimately tooth loss if left untreated [1, 2]. Disease onset and progression are strongly associated with a microbial shift from symbiotic to dysbiosis communities, where major pathogens such as Porphyromonas gingivalis gain an ecological advantage and activate a chronic inflammatory cascade. These pathogens disrupt periodontal homeostasis by releasing virulence factors that damage the epithelial barrier, subvert immune clearance, and promote connective tissue degradation [3].

The conceptual model of periodontitis has evolved from a simplistic infectious-disease paradigm to one that recognizes the complex interplay between pathogenic microbial communities and host immune responses. Professional mechanical plaque removal (PMPR), as defined in the EFP S3-level guideline, is a fundamental component of non-surgical periodontal therapy [4, 5]. However, recognized limitations of PMPR in disrupting complex subgingival biofilm ecosystems, particularly in deep or anatomically challenging periodontal pockets, have prompted interest in adjunctive therapeutic approaches. These strategies extend beyond bacterial reduction and aim to re-establish a balanced microbial environment while modulating host immune responses to support long-term periodontal stability [3, 6]. Among these approaches, probiotics have been investigated as potential adjunctive agents capable of influencing microbial composition and host inflammatory pathways while avoiding concerns related to antibiotic resistance [3, 7].

Probiotics are viable microorganisms that, when delivered in sufficient quantities, exert beneficial effects on the host’s health, often by modulating the local microbiota and immune response. Their mechanism of action includes competitive inhibition of pathogenic bacteria, enhancement of epithelial barrier integrity, and downregulation of pro-inflammatory cytokines [6, 8]. The many probiotic strains studied for periodontal use, including Lactobacillus plantarum and Lactobacillus brevis, have shown the most consistent benefits in both in vitro and in vivo models. These strains exhibit antimicrobial activity against major pathogens, such as Porphyromonas gingivalis, as well as anti-inflammatory effects and support for tissue regeneration [9].

The European Federation of Periodontology (EFP) developed S3-level clinical practice guidelines for the treatment of periodontitis using a rigorous methodology based on the GRADE framework. These guidelines provide stage-specific, evidence-based recommendations aligned with the 2017 classification of periodontal diseases. For stages I–III, a stepwise therapeutic approach is recommended, beginning with behavioural modification and supra- and subgingival instrumentation, followed by adjunctive therapies and, when indicated, surgical intervention, as outlined by Sanz et al. (2020). In 2022, Herrera et al. further addressed the additional complexity of Stage IV periodontitis, emphasizing functional sequelae such as tooth loss, pathologic migration, and occlusal instability, which often necessitate an interdisciplinary treatment strategy integrating periodontal, prosthodontic, orthodontic, and implant-based therapies. Overall, the EFP S3-level guidelines provide a comprehensive, evidence-based framework to support systematic, stage-adapted management of periodontitis [4, 5].

Biologically based adjuncts are increasingly investigated in periodontal therapy due to their potential to influence the oral microbiome and host immune responses. Probiotics have been explored as adjunctive strategies to promote microbial balance while modulating inflammatory pathways, without the drawbacks of systemic antimicrobials [3, 6]. Experimental and clinical studies suggest that certain probiotic strains can inhibit pathogenic species, modulate cytokine expression, and support epithelial barrier integrity. Lactobacillus species have received particular attention in oral health research due to their antimicrobial and immunomodulatory properties. These bacteria produce antimicrobial compounds such as organic acids, bacteriocins, and hydrogen peroxide, which may suppress periodontal pathogens [2, 10]. Selected Lactobacillus strains have also been associated with the modulation of inflammatory mediators and support of mucosal integrity [3]. Lactobacillus plantarum and Lactobacillus brevis have been investigated for their potential antimicrobial and immunomodulatory properties in both experimental models and clinical trials [11, 12]. Their proposed dual action on microbial suppression and host response modulation has led to their evaluation as adjuncts to non-surgical periodontal therapy [13]. This systematic review critically assesses the available clinical evidence on the adjunctive use of Lactobacillus plantarum and Lactobacillus brevis in the management of periodontitis.

Materials and methods

This study was conducted as a systematic review and registered in the PROSPERO database (CRD420251039344). A comprehensive literature search was conducted across Scopus, SAGE Journals, ScienceDirect, PubMed, and ProQuest, covering publications from January 2020 to April 2025. The search strategy was adapted to each database’s syntax and indexing system while maintaining consistent Boolean logic across platforms. The search combined the following key concepts: periodontitis, probiotics (including Lactobacillus plantarum and Lactobacillus brevis), and non-surgical periodontal therapy (professional mechanical plaque removal [PMPR] and scaling and root planing [SRP]). The complete set of database-specific search strings is provided in Appendix A. Where available, database filters for language (English) and study design (randomized controlled trials) were applied during the search process. The search was last updated on 20 April 2025. In databases where such filters were unavailable, eligibility was assessed during title–abstract and full-text screening using predefined inclusion and exclusion criteria.

Studies were eligible if they met the following inclusion criteria: (1) randomized controlled clinical trials; (2) participants diagnosed with periodontitis according to the 1999 or 2017 World Workshop classifications; (3) adjunctive administration of Lactobacillus plantarum and Lactobacillus brevis following PMPR; (4) reporting clinical outcomes including probing pocket depth (PPD), clinical attachment level (CAL), or other periodontal parameters; and (5) follow-up duration between 1 and 9 months. Only full-text articles published in English were included. Studies were excluded if they were in vitro, animal, case reports, review articles, conference abstracts, or did not report relevant clinical outcomes. Trials involving concurrent systemic antibiotic therapy or surgical periodontal interventions during the study period were also excluded. The research question in this study was “How is the effectiveness of probiotics Lactobacillus plantarum and Lactobacillus brevis applied in several forms, such as subgingival gel and lozenges, as adjuncts to PMPR, compared to PMPR alone or PMPR with placebo in patients with periodontitis?“. This research question is formulated using the PICO framework, which comprises Population, Intervention, Comparison, and Outcome. A table of PICO descriptions is provided in Table 1. From the PICO analysis, keywords can be arranged using periodontitis, lactobacillus plantarum, lactobacillus brevis, and non-surgical therapy.

Table 1.

PICO description

Population	Interventions	Comparison	Outcome
Patients with periodontitis, (based on 2017 World Workshop Classification) Age range: 10–80 years	Administration of probiotics Lactobacillus plantarum and Lactobacillus brevis in several forms, such as subgingival topical gel, and lozenges, as adjuncts to PMPR.	Control group receiving non-surgical periodontal therapy: PMPR alone or PMPR + placebo.	Primary Outcome : - PPD Secondary Outcome - CAL - BOP - Gingival Index - Gingival bleeding index - Plaque Index

Research identification and selection

The research was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. A flow chart is provided in Table 2. Research identification began on 10 February 2025 by searching five electronic databases: Scopus, SAGE Journals, ScienceDirect, PubMed, and ProQuest. The search combined the following key concepts: periodontitis, probiotics (including Lactobacillus plantarum and Lactobacillus brevis), and non-surgical periodontal therapy, including professional mechanical plaque removal (PMPR) and scaling and root planing (PMPR).

Table 2.

Qualitative synthesis results

Author (Year)	Number of participants	Intervention	Periodontal Conditions	Clinical Parameters	Follow-up Duration	Result
Ibrahim et al. (2024)	22 patients (11 in PMPR + Probiotics group, 11 in PMPR only group)	Group I: PMPR + single-dose subgingival probiotic gel. Group II: PMPR only	Patients diagnosed with Stage III, Grade C periodontitis, molar-incisor pattern	- PPD - Plaque Index - CAL - Gingival Index	3 months, 6 months, and 9 months	↓ PI, GI, PPD, CAL the difference between groups was not statistically significant.
Nasr et al. (2023)	18 female patients were divided randomly into two equal groups.	Group I: PMPR + single-dose subgingival probiotic gel. Group II: PMPR only	Patients with Stage I or II Grade A periodontitis, PPD ≤ 5 mm	- PPD - CAL - Plaque Index (PI) - Gingival Index (GI)	1 month and 3 months	↓ PPD, CAL the difference between groups was statistically significant.
Pudgar et al. (2020)	40 patients who received PMPR were divided randomly into two equal groups.	Group I: PMPR + single-dose subgingival probiotic gel + daily probiotic lozenges (3 months) Group II: PMPR only	Periodontitis stage III / IV with a probing depth (PD) of ≥ 5 mm	- PPD - CAL - BOP - Plaque index - Gingival bleeding index	3 months	↓ GBI, but this group also had a higher number of residual diseased sites compared to the placebo group.

GBI Gingival Bleeding Index, PPD Periodontal Probing Depth, CAL Clinical Attachment Loss, BOP Bleeding On Probing

↑ indicates increase; ↓ indicates decrease

The search results from the five electronic databases with these keywords yielded 157 studies: 30 from Scopus, 4 from SAGE Journals, 20 from ScienceDirect, 30 from PubMed, and 73 from ProQuest (Fig. 1). The studies identified through the manual data search are 2. All studies were deduplicated in Microsoft Excel, and 9 were identified as duplicates. Title and abstract screening was conducted for 150 studies; 143 were excluded for failing to meet the inclusion and exclusion criteria. The remaining seven studies were then reviewed in full text. From reading the full manuscripts, a total of four studies were excluded for the following reasons: one study used probiotic strains other than Lactobacillus plantarum or Lactobacillus brevis; one study utilized additional active interventions such as light-activated disinfection (LAD), making it difficult to isolate the effect of probiotics; one study involved the use of probiotic mouthwash with a different strain focus and targeted microbial outcomes rather than clinical parameters; and one study lacked strain specificity and did not clearly report the clinical effectiveness of the probiotic intervention.

Fig. 1.

PRISMA flow diagram of the review

Data synthesis

A quantitative meta-analysis was not performed due to substantial clinical and methodological heterogeneity across the included trials. Differences were observed in disease stage (Stage I–II, Stage III Grade C, and Stage III-IV), probiotic administration protocols (subgingival gel alone vs. subgingival gel combined with lozenges), follow-up time points (ranging from 1 to 9 months), and outcome reporting formats. Notably, one study reported median (IQR) values rather than mean ± SD, precluding standardized effect-size calculation. Therefore, a structured narrative synthesis was conducted.

Results

Characteristics of the selected studies

All three studies included in this systematic review were randomized controlled clinical trials. One study was conducted in Egypt [14], one in Iraq [15], and one in Slovenia [16]. A summary of the study characteristics is provided in Table 2.

Characteristics of interventions

Of the three included studies, all evaluated the efficacy of Lactobacillus plantarum and Lactobacillus brevis as adjuncts to non-surgical periodontal therapy (PMPR). Nasr et al. administered a subgingival topical probiotic gel containing both strains immediately after PMPR into periodontal pockets [14]. Ibrahim et al. also applied a subgingival topical probiotic gel containing the same strains at molar-incisor sites following PMPR, with applications sustained across multiple follow-up points [15]. Pudgar et al. combined a single application of subgingival probiotic gel with daily oral administration of probiotic lozenges containing L. plantarum and L. brevis for 30 days [16]. All three interventions aimed to enhance periodontal healing by modulating inflammation and microbial composition in conjunction with mechanical debridement.

Characteristics of outcome measures

All three included studies evaluated probing pocket depth (PPD) and clinical attachment level (CAL) as primary clinical outcomes (Tables 2 and 3). Nasr and Pudgar additionally assessed gingival bleeding using the Gingival Bleeding Index (GBI), whereas Ibrahim and Nasr evaluated plaque accumulation and gingival inflammation through the Plaque Index (PI) and Gingival Index (GI) [14–16]. Only Nasr investigated biochemical markers in gingival crevicular fluid, specifically interleukin-10 (IL-10) and osteoprotegerin (OPG), to assess modulation of the host inflammatory response. Ibrahim additionally performed microbiological analysis by quantifying Aggregatibacter actinomycetemcomitans using quantitative PCR [14]. In all studies, PPD and CAL were measured using a periodontal probe at six sites per tooth, excluding third molars. Inflammatory parameters, such as GI, GBI, and bleeding on probing (BOP), were recorded as percentage-based indices or dichotomous (present/absent) measures, depending on the study protocol.

Table 3.

Results of individual studies for PPD and CAL

Author (Year)	Outcome	Time point	n (Test)	Mean ± SD (Test)	n (Control)	Mean ± SD (Control)	Mean Difference (Test–Control)	Data Availability Notes
Ibrahim et al. (2024)	PPD (mm)	Baseline	11	6.864 ± 1.052	11	6.673 ± 1.011	+ 0.191	-
		3 months	11	4.655 ± 0.758	11	5.145 ± 0.927	-0.490	-
		6 months	11	4.082 ± 0.618	11	4.627 ± 0.980	-0.545	-
		9 months	11	3.782 ± 0.732	11	4.155 ± 1.020	-0.373	-
	CAL (mm)	Baseline	11	5.818 ± 0.733	11	5.682 ± 0.926	+ 0.136	-
		3 months	11	4.791 ± 0.737	11	4.945 ± 0.758	-0.154	-
		6 months	11	4.418 ± 0.801	11	4.655 ± 0.767	-0.237	-
		9 months	11	3.982 ± 0.835	11	4.382 ± 0.952	-0.400	-
Nasr et al. (2023)	PPD (mm)	Baseline	9	4.09 ± 0.9	9	3.90 ± 0.9	+ 0.19	-
		1 months	9	2.64 ± 0.5	9	2.66 ± 0.5	-0.02	-
		3 months	9	2.13 ± 0.6	9	2.53 ± 0.4	-0.40	Significant (p = 0.040)
	CAL (mm)	Baseline	9	2.67 ± 0.7	9	2.28 ± 0.8	+ 0.39	-
		1 months	9	1.26 ± 0.9	9	1.43 ± 0.8	-0.17	-
		3 months	9	0.73 ± 0.1	9	1.38 ± 0.7	-0.65	Significant (p = 0.026)
Pudgar et al. (2021)	PPD (mm)	Baseline	20	Median 3.96	20	Median 4.03	Not calculable	Reported as median (IQR); mean ± SD not available
		3 months	20	Median 3.04	20	Median 3.13	Not calculable	Effect estimate cannot be derived
	CAL (mm)	-	-	Not extractable as mean ± SD	-	-	Not calculable	Only median-based reporting

Statistical significance was defined as p < 0.05

Characteristics of outcomes

All three included trials reported improvements in periodontal clinical parameters following non-surgical periodontal therapy (PMPR), with or without adjunctive probiotic administration. Nasr et al. reported significant reductions in probing pocket depth (PPD) and clinical attachment level (CAL) in both groups over time, with statistically greater intergroup improvements observed in the probiotic group at the 3-month follow-up. In addition, IL-10 levels were significantly higher in the probiotic group than in the control group, suggesting enhanced anti-inflammatory modulation, whereas no statistically significant intergroup differences were observed for osteoprotegerin (OPG) [14]. Ibrahim et al. similarly observed significant intragroup reductions in PPD and CAL in both test and control groups. Although mean clinical values numerically favored the probiotic group across follow-up timepoints, no statistically significant intergroup differences were detected. A reduction in Aggregatibacter actinomycetemcomitans levels was reported in the probiotic group; however, between-group differences were not statistically significant [15]. Pudgar et al. demonstrated significant intragroup improvements in both probiotic and placebo groups for PPD, CAL, bleeding on probing (BOP), gingival bleeding index (GBI), and plaque index. However, no statistically significant intergroup differences were observed for PPD, CAL, or BOP at the 3-month follow-up. Although the probiotic group showed a numerically greater reduction in GBI, it also had a higher number of residual diseased sites (PD > 4 mm + BOP) than the placebo group [16].

Risk of bias assessment

The Cochrane risk-of-bias instrument for randomised trials (RoB 2), Version 2, was used to assess the risk of bias for randomised clinical trials. It has five categories, with assessment findings classified as having a low risk of bias. Both a modest chance of prejudice and a concern exist. Two studies were determined to have a low risk of bias, and one study was determined to have a moderate risk of bias based on the findings of the risk of bias evaluation. The risk of bias assessment’s findings are displayed in Fig. 2. The risk of bias assessment was performed using the Cochrane Risk of Bias 2 (RoB2) tool across five domains. Two studies were judged as having low risk of bias overall, while one study presented some concerns primarily related to allocation concealment and protocol registration. No study demonstrated high risk of bias in any domain. Most domains were rated as low risk, particularly for missing outcome data and outcome measurement, reflecting adequate reporting and standardized periodontal assessment methods as shown as in Table 4.

Fig. 2.

The results of the risk of bias assessment using the Cochrane risk of bias 2 (RoB2) tool

Table 4.

Risk of bias assessment using RoB 2 tool

Author (Year)	Randomization Process (D1)	Deviations from Intended Interventions (D2)	Missing Outcome Data (D3)	Measurement of the Outcome (D4)	Selection of the Reported Result (D5)	Overall Risk	Rationale Summary
Ibrahim et al. (2024)	Some concerns	Low risk	Low risk	Low risk	Some concerns	Some concerns	Randomization mentioned but allocation concealment not clearly described. No reported protocol deviations. Outcome data complete with no attrition. Clinical parameters measured using standardized periodontal probing. Lack of prior protocol registration introduces potential selective reporting bias.
Nasr et al. (2023)	Low risk	Low risk	Low risk	Low risk	Some concerns	Low risk	Random allocation described and baseline characteristics comparable. No major deviations from intervention protocol. No missing data reported. Periodontal measurements performed using standardized clinical methods. Study protocol not publicly registered, raising minor concerns regarding selective reporting.
Pudgar et al. (2021)	Low risk	Some concerns	Low risk	Low risk	Low risk	Some concerns	Randomization was adequately described. The use of combined probiotic delivery (gel and lozenges) may introduce performance variability between intervention components. No significant missing outcome data were reported. Clinical measurements were conducted using standardized and calibrated periodontal assessment methods. Outcomes were reported according to the prespecified study objectives.

Certainty of evidence

The certainty of evidence for each outcome was evaluated using the GRADE approach. Overall, the certainty of evidence was rated as low for PPD reduction, CAL gain, and gingival bleeding parameters due to imprecision, small sample sizes, and clinical heterogeneity. The certainty of evidence for IL-10 levels was rated as very low, as it was based on a single small study with short-term follow-up. A detailed summary of the findings and reasons for the downgrade is presented in Table 5.

Table 5.

Summary of findings and certainty of evidence

Outcome	No. of Studies	Effect Direction	Certainty of Evidence	Reason for Downgrading
PPD reduction	3 RCTs	Inconsistent intergroup effects	Low	Small sample sizes, heterogeneity in probiotic delivery and disease severity
CAL gain	3 RCTs	Mixed results	Low	Imprecision, short follow-up duration (≤ 3 months)
Gingival bleeding parameters	2 RCTs	Variable improvement	Low	Inconsistent intergroup statistical significance
IL-10 levels	1 RCT	Increased in probiotic group	Very Low	Single study, small sample size, short-term follow-up

Certainty of evidence was assessed using the GRADE approach. Evidence was downgraded due to risk of bias, inconsistency, imprecision, and clinical heterogeneity. “Low” and “Very Low” indicate limited and very limited confidence in the effect estimate, respectively

Discussion

Periodontitis is a chronic, multifactorial, biofilm-induced inflammatory disease that affects the supporting structures of the teeth, including the gingiva, periodontal ligament, cementum, and alveolar bone [17]. The pathogenesis of periodontitis begins with the accumulation of pathogenic microbial biofilms on the tooth surface, which triggers a sustained immune-inflammatory response. Although microbial colonization is a necessary trigger, the severity and progression of periodontal destruction are primarily determined by the magnitude and dysregulation of the host response. This immunoinflammatory imbalance leads to degradation of connective tissue attachment and alveolar bone resorption, ultimately resulting in tooth loss if left untreated [18]. An important feature of this process is the ecological shift from a symbiotic to a dysbiotic subgingival microbiota, dominated by gram-negative anaerobes such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. These key pathogens evade host defences and subvert the immune system, creating a self-sustaining pathogenic microenvironment [19]. The concept of dysbiosis underscores that effective periodontal therapy must go beyond mechanical debridement, but also include strategies capable of modulating the microbial community and host response. Therefore, current research efforts are increasingly focusing on biologically driven adjunctive therapies, such as probiotics, which can help restore microbial homeostasis and reduce pathological inflammation in the periodontal environment [12].

Professional mechanical plaque removal (PMPR), as recommended in the EFP S3-level clinical practice guideline, constitutes the cornerstone of non-surgical periodontal therapy and represents the standard initial treatment approach [4, 5]. This intervention involves thorough debridement of supragingival and subgingival deposits to disrupt pathogenic biofilm and remove calculus from root surfaces [20]. The primary objective is to create a biologically compatible root surface that facilitates periodontal healing and reduces clinical signs of inflammation, including probing depth and bleeding. PMPR has been demonstrated to be effective in controlling microbial burden and reducing inflammatory progression; however, certain limitations remain. Mechanical therapy alone may not fully eliminate subgingival pathogens in anatomically complex sites, nor may it completely restore microbial homeostasis or resolve host inflammatory dysregulation [12]. These therapeutic limitations have prompted investigation into adjunctive strategies aimed at enhancing microbial modulation and host response regulation. Among these, probiotics have been explored as potential adjunctive agents that can influence the subgingival microbiota and modulate inflammatory pathways [13].

Probiotics are live microorganisms that confer health benefits to the host when applied in adequate amounts [21]. Their application in periodontal therapy is based on their potential to influence microbial balance and modulate the dysregulated immune response characteristic of periodontitis [22]. Among the diverse probiotic genera, Lactobacillus species are among the most extensively investigated in oral health research, owing to evidence suggesting their ability to suppress periodontal pathogens, support epithelial barrier integrity, and modulate host immune responses through anti-inflammatory pathways. These microorganisms may contribute to ecological stability within the oral cavity by producing antimicrobial compounds, lowering environmental pH, and competing with pathogenic bacteria for adhesion sites and nutrients. Additionally, certain Lactobacillus strains have been associated with the modulation of cytokine expression, including attenuation of pro-inflammatory mediators [3].

Accordingly, probiotics have been investigated as adjunctive agents in periodontal therapy, particularly in combination with conventional mechanical treatment such as PMPR [13]. However, it is important to recognize that Lactobacillus species are not dominant constituents of the native subgingival microbiota. Their therapeutic effects are therefore more likely to be mediated through transient functional interactions such as immune modulation, metabolic signalling, and biofilm interference rather than permanent colonization or the restoration of the original microbial composition. Among the various Lactobacillus species explored for periodontal application, Lactobacillus brevis and Lactobacillus plantarum have demonstrated particular relevance due to their well-documented biological properties that align with the therapeutic needs of periodontal healing [15, 16]. Both strains have shown robust antimicrobial activity against anaerobic periodontal pathogens, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, through the secretion of bacteriocins and the production of organic acids, such as lactic acid [22]. In addition to their antimicrobial function, these probiotics are recognized for their immunomodulatory capacity [15]. According to experimental evidence, L. brevis and L. plantarum inhibit pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) and increase the synthesis of interleukin-10 (IL-10), which in turn promotes anti-inflammatory responses [22]. Moreover, both strains support mucosal barrier integrity by regulating epithelial tight junction proteins and reducing oxidative stress, which are critical for the prevention of further tissue breakdown in periodontal lesions, as shown in Fig. 3 [3, 23].

Fig. 3.

Pathways of host–microbiome modulation by Lactobacillus strains in periodontal disease resolution. HYA (10-hydroxy-cis-12-octadecenoic acid) ; BMP (Bone Morphogenetic Protein) ; RANKL (Receptor Activator of Nuclear Factor-κB Ligand) ; GABA (Gamma-aminobutyric acid) ; KetoC (10-oxo-trans-11-oxadecenoic acid) ; EMVs (Nano-sized extracellular membrane vesicles) ; MIMP (Micro integral membrane protein); (created with BioRender.com).

Experimental studies have shown that Lactobacillus plantarum and Lactobacillus brevis may exert antimicrobial, anti-inflammatory, and barrier-protective effects by modulating host immune signaling pathways, including suppression of NF-κB activation, regulation of pro- and anti-inflammatory cytokines, and interference with osteoclastogenic signaling. These biological mechanisms provide theoretical plausibility for the modest clinical improvements observed in early-stage disease. However, it should be emphasized that the included clinical trials did not directly assess these molecular pathways; therefore, these mechanistic considerations should be interpreted as supportive background rather than direct clinical evidence [3, 11, 24, 25]. Due to this combination of antimicrobial, anti-inflammatory, and barrier-protective effects, L. brevis and L. plantarum are regarded as promising adjuncts in the management of periodontitis, with the potential to complement and enhance the outcomes of conventional mechanical therapy [14–16].

Three clinical trials included in this systematic review evaluated the adjunctive use of Lactobacillus brevis and Lactobacillus plantarum alongside PMPR in the treatment of periodontitis. Although all three studies used the same probiotic strains, their findings diverged regarding clinical efficacy, immunological responses, and microbial changes, potentially due to differences in probiotic application methods, treatment durations, and disease stages. Each study assessed clinical parameters such as probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and gingival index (GI), with some also investigating immunological or microbiological markers. Notably, although one study reported statistically significant improvements in both clinical and immunological outcomes, others observed more modest or nonsignificant differences between test and control groups [14–16].

The divergent findings among the three included trials highlight the influence of clinical and methodological heterogeneity on treatment outcomes. Although all trials used the same probiotic strains, they differed in disease stage (early vs. advanced), delivery strategy (localized subgingival gel application alone versus subgingival gel combined with oral probiotic lozenges), dosage regimen, and follow-up duration. These differences likely contributed to the observed variability in intergroup effects. Notably, Nasr et al., which focused on early-stage periodontitis with localized subgingival delivery, demonstrated the most pronounced intergroup improvements. In contrast, studies targeting advanced disease stages (Stage III–IV) did not show significant additive benefits. Collectively, these findings suggest that probiotic efficacy may be influenced by baseline disease severity and delivery protocol characteristics rather than solely by strain selection (Table 6).

Table 6.

Summary of probiotic application, dosage, and clinical outcomes in studies on L. brevis and L. plantarum as adjuncts in periodontal therapy

Author (Year)	Probiotic Application	Dosage & Duration	Evaluated Parameters	Result	p-value	Statistical Conclusion	Brief Interpretation
Ibrahim et al. (2024)	Subgingival probiotic gel	1 application (single dose)	IL-10 (baseline vs. 1 month)	↑ IL-10	p < 0.05	Meaningful intra-group change	IL-10 improved in the probiotic group only, not vs. control
			TNF-α (baseline vs. 1 month)	↓ TNF-α	p < 0.05	Biologically relevant shifting	TNF-α dropped in the probiotic group, not between groups
			PPD, CAL, PI, GI (baseline vs. 3–9 months)	All improved in the probiotic group	p < 0.05 (within); p > 0.05 (between)	Improvement only in the intra-group	Positive changes occurred only when compared to baseline, not superior to the control group
Nasr et al. (2023)	Subgingival probiotic gel	1 application (single dose)	IL-10 (1 month)	↑ IL-10	p = 0.002	Statistically meaningful between groups	IL was − 10 significantly higher in the probiotic group
			OPG (1 month)	↑ OPG	p = 0.166	No reliable difference	Numerical increase, not statistically supported
			PPD (3 months)	↓ PPD	p = 0.040	Marked difference	The probiotic group had lower PPD than the control group
			CAL (3 months)	↓ CAL	p = 0.026	Confirmed differences	CAL gains the better in probiotic group
Pudgar et al. (2021)	Subgingival probiotic gel + Lozenges	1 application probiotic gel (single dose) + Lozenges (daily for 3 months)	GBI (3 months)	↓ GBI	p = 0.048	Clinically relevant	GBI has decreased in the probiotic group
			Diseased sites (DS)	More DS in probiotic group	p < 0.001	Statistically clear, but negative	More residual disease in the probiotic group
			Healing sites	Fewer heated sites in probiotic group	p < 0.001	Direction opposite to expectation	Healing significantly lower in probiotic group
			PPD (3 months)	No meaningful difference	p = 0.882	Not statistically significant	No advantage of probiotics on PPD reduction
			CAL (3 months)	No meaningful difference	p = 0.310	Not statistically significant	CAL improvement similar in both groups

delete this row!

GBI Gingival Bleeding Index, PPD Periodontal Probing Depth, CAL Clinical Attachment Loss

Statistical significance was defined as p < 0.05

↑ indicates increase; ↓ indicates decrease

Nasr et al. demonstrated the greatest intergroup improvements, which may be associated with the inclusion of patients with early-stage periodontitis and the use of localized subgingival probiotic delivery. In contrast, studies conducted in advanced disease stages (Stage III–IV), including those by Ibrahim and Pudgar, did not report significant additive intergroup benefits despite employing similar or combined delivery strategies. These findings suggest that baseline disease severity may substantially influence therapeutic responsiveness [14–16]. Early-stage periodontitis may provide a more favorable biological environment for microbial modulation and tissue repair, whereas stage III-IV periodontitis is characterized by structural damage, complex dysbiosis, and extensive attachment loss, which contributes to pathological tooth migration, thereby reducing the sensitivity and representativeness of conventional probing-based parameters [4, 5].

Beyond disease stage and delivery method, intrinsic characteristics of the probiotic strains themselves may also contribute to the variability in clinical outcomes. Evidence from probiotic trials across different indications shows that efficacy is both strain‑specific and stage‑specific, underscoring that not all probiotic strains or formulations perform equally well [26]. Although Lactobacillus plantarum and Lactobacillus brevis have possible antimicrobial and immunomodulatory properties, Lactobacilli are not inherently dominant members of the subgingival microbial community, which is better understood as a context‑dependent dysbiosis polymicrobial assemblage rather than a disease driven by single pathogens [3, 24, 25]. Their ecological compatibility, persistence, and interaction with the resident community may therefore influence whether a given strain yields measurable clinical benefit. This consideration partly explains why outcomes differ among studies and highlights the need for careful strain selection and ecological rationale in future investigations [27].

Despite differences in intergroup outcomes, all three studies reported intragroup clinical improvements following PMPR, reaffirming the established efficacy of mechanical debridement as the cornerstone of periodontal treatment. Parameters such as plaque index and gingival index improved regardless of probiotic administration, underscoring the foundational role of PMPR in controlling supragingival biofilm and inflammation [7]. In contrast, deeper clinical parameters, including probing pocket depth reduction, attachment level gain, and modulation of host immune markers such as IL-10, were reported in one study employing subgingival delivery in early-stage disease [14].

Methodological heterogeneity across trials limits direct comparison. The small number of included studies, variations in probiotic dosage and delivery strategy, and inconsistent reporting of microbiological and immunological outcomes restrict the strength and generalizability of conclusions. Short follow-up durations further limit assessment of long-term sustainability [14–16].

Future research should prioritize standardized clinical protocols, adequate sample sizes, and longer follow-up periods. Incorporation of molecular and immunological assessments may help clarify potential mechanisms underlying observed clinical changes. Stratification by disease stage and baseline clinical characteristics may further refine understanding of which patient subgroups are most likely to benefit. Overall, current evidence suggests potential benefits of Lactobacillus brevis and Lactobacillus plantarum as adjunctive agents in periodontal therapy, with more favourable outcomes reported in early-stage disease when delivered subgingival. However, given the limited and heterogeneous evidence base, probiotics should be regarded as potential complements rather than replacements for established mechanical therapy.

Conclusions and future perspectives

Three randomized clinical studies were used in this systematic review to evaluate the adjunctive use of Lactobacillus brevis and Lactobacillus plantarum in non-surgical periodontal therapy. Although all studies used the same probiotic strains, clinical outcomes varied depending on the delivery method, disease stage, and treatment duration. Among the various probiotic delivery methods evaluated, subgingival topical probiotic gel showed the most consistent and favourable short-term outcomes, reflected by significant reductions in PPD and CAL, as well as elevated levels of anti-inflammatory mediators such as IL-10. In contrast, systemic and combined delivery applications showed limited or nonsignificant effects over PMPR alone in stage III-IV periodontitis. These findings highlight that the effectiveness of adjunctive subgingival probiotic therapy may vary across clinical contexts. Furthermore, the current evidence indicates that adopting a personalized approach to adjunctive probiotic therapy, considering factors such as disease stage, delivery method, and periodontal conditions, can be beneficial by identifying who is likely to benefit most from this treatment.

Despite these observations, the conclusions of this systematic review are constrained by the limited number of randomized clinical trials and the relatively small sample sizes of the included studies. As only three trials met the inclusion criteria, the overall evidence supporting the use of probiotic adjuncts in periodontitis remains heterogeneous and insufficient to draw definitive conclusions. Future research should prioritize well-designed, adequately powered randomized controlled trials with standardized probiotic formulations, involve larger patient cohorts, clearly defined outcome measures, and extended follow-up periods to produce more robust and generalizable findings.

Appendix

Appendix A. Search strategy

Database	Search String	Result
Scopus	TITLE-ABS-KEY (periodontitis) AND TITLE-ABS-KEY (probiotic OR “Lactobacillus plantarum” OR “Lactobacillus brevis”) AND TITLE-ABS-KEY (“non-surgical periodontal therapy” OR “professional mechanical plaque removal” OR PMPR OR “scaling and root planing” OR SRP)	30
SAGE Journals	(periodontitis) AND (probiotic OR “Lactobacillus plantarum” OR “Lactobacillus brevis”) AND (“non-surgical periodontal therapy” OR “professional mechanical plaque removal” OR PMPR OR “scaling and root planing” OR SRP)	4
ScienceDirect	(periodontitis) AND (probiotic OR “Lactobacillus plantarum” OR “Lactobacillus brevis”) AND (“non-surgical periodontal therapy” OR “professional mechanical plaque removal” OR PMPR OR “scaling and root planing” OR SRP)	20
PubMed	(“Periodontitis“[MeSH Terms] OR periodontitis[Title/Abstract]) AND (“Probiotics“[MeSH Terms] OR probiotic[Title/Abstract] OR “Lactobacillus plantarum“[Title/Abstract] OR “Lactobacillus brevis“[Title/Abstract]) AND (“non-surgical periodontal therapy“[Title/Abstract] OR “professional mechanical plaque removal“[Title/Abstract] OR PMPR[Title/Abstract] OR “scaling and root planing“[Title/Abstract] OR SRP[Title/Abstract])	30
ProQuest	(periodontitis) AND (probiotic OR “Lactobacillus plantarum” OR “Lactobacillus brevis”) AND (“non-surgical periodontal therapy” OR “professional mechanical plaque removal” OR PMPR OR “scaling and root planing” OR SRP)	73

Authors’ contributions

Author’s contributions: R.G.A.P, B.S, Y.S, C.W.C, and D.I.H designed the study. R.G.A.P and B.S, investigated and performed the study. R.G.A.P, B.S evaluated the risk of bias assessment. Y.S, and D.I.H validated the result. R.G.A.P, B.S, Y.S, C.W.C, and D.I.H wrote the manuscript. All author proofed the final manuscript.

Funding

None.

Data availability

The datasets used and/or analyzed during the current study 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.