Adjunctive benefit of probiotic supplementation along with nonsurgical therapy for peri-implant diseases – A systematic review and meta-analysis

Abstract

Peri-implant diseases are prevalent conditions, but a predictable management strategy is still lacking. The objective of the present article was to evaluate the adjunctive benefits of probiotics with nonsurgical therapy in the management of peri-implant diseases. The review protocol was registered in PROSPERO and prepared according to PRISMA guidelines. Randomized controlled clinical trials in patients diagnosed with the peri-implant disease where probiotic was used as an adjunct to nonsurgical therapy were included in the study. The risk difference of percentage reduction in bleeding on probing, plaque accumulation, and mean difference in probing pocket depth reductions at implant level were estimated using a random effect model due to high heterogeneity among studies. Four studies fulfilled the criteria for selection. Two of them presented data on both peri-implantitis and peri-implant mucositis and they were considered separate studies during meta-analysis. Significant reduction in percentage of bleeding on probing was noticed at 1 and 3 months (−0.28 [−0.48, −0.09], P = 0.004 and − 0.19 [−0.35, −0.02], P = 0.03, respectively), but the reduction was not statistically significant at 6 months. Similar results were also observed for plaque accumulation. No statistically significant reduction in probing pocket depth was observed in the probiotic group during any of the re-evaluations.

Conclusion:

Adjunctive therapy of probiotics may improve the efficacy of nonsurgical therapy of peri-implant diseases for up to 3 months. However, moderate certainty was observed for a reduction in bleeding on probing after 1-month re-evaluation alone.

INTRODUCTION

Dental implants are currently considered an acceptable and predictable solution for replacing missing teeth. With the increased prevalence of implant placement, the number of associated complications is also rising. Microbial plaque accumulation around the implants initiates inflammation in the peri-implant soft tissue resulting in peri-implant mucositis. When left untreated, it can progress to peri-implantitis. The prevalence of peri-implant diseases is increasing worldwide and can also increase as a function of time.[1-3] Poor oral hygiene can predispose to peri-implantitis creating an increased risk of 3–14 times.[4] Professionally and personally administered plaque control can prevent peri-implant diseases to a greater extent.[5]

Currently, definite guidelines are not available regarding the management of peri-implant diseases. Due to the similarity in pathogenesis with periodontal disease, therapeutic strategies that are found to be successful in the management of gingivitis and periodontitis are thought to be beneficial for peri-implant diseases as well. The cornerstone of periodontal therapy is nonsurgical approaches comprising scaling and root debridement, oral hygiene instructions, and the use of antimicrobial agents. Recently, many new nonsurgical approaches have emerged in the management of periodontal disease which include probiotics, host modulation, and photodynamic therapy and many of them appear to be promising adjuncts to create a healthy periodontium.

Probiotics are defined by the Food Agricultural Organization/World Health Organization as “living micro-organisms which, when administered in adequate amounts, confer a health benefit to the host by suppressing endogenous and exogenous pathogens and by promoting beneficial host response.”[6] It acts through the prevention of adhesion of pathogenic species, inhibition of bacterial growth, modulation of the mucosal immune system by decreasing the production of inflammatory mediators or by altering cell proliferation, and improvement of intestinal barrier integrity.[7] Lactobacillus or Bifidobacterium genera are commonly used to treat different diseases including oropharyngeal infections.[8] A recent systematic review and meta-analysis demonstrate the beneficial effects of probiotics as an adjunct to nonsurgical periodontal therapy in reducing pocket depth, especially in the case of deep pockets in chronic periodontitis patients.[9]

The usefulness of nonsurgical mechanical debridement in managing gingivitis is proved beyond suspicion, and so is the case of peri-implant mucositis. However, the complete resolution is not achieved with mechanical debridement alone in many cases of peri-implant mucositis.[5] The added benefits of other novel nonsurgical adjuncts like probiotics in peri-implant mucositis are still not clear. A previous systematic review concluded that adjunctive therapy like systemic or local antibiotics or antiseptics does not confer any adjunctive benefits in decreasing gingival bleeding or pocket depth at mucositis sites.[5] Since no predictable treatment option is available for peri-implantitis, more emphasis should be placed on the treatment of its precursor, peri-implant mucositis to achieve secondary prevention.[10] New adjunct measures also must be identified to improve the efficacy of existing therapeutic modalities.

Even though a few studies have evaluated the influence of probiotics in the management of peri-implant diseases, they present conflicting results.[11,12] Few systematic reviews were also published, but they did not provide adequate evidence.[13-15] This systematic review is aimed at summarizing the currently available evidence regarding the adjunctive use of probiotics along with nonsurgical therapy in the management of peri-implant diseases.

METHODS

This systematic review protocol was registered in PROSPERO[16] and was prepared according to PRISMA guidelines.[17]

Focus question

Focus question was prepared based on the participants, intervention, comparison, outcomes, and study design (PICOS) format. The question was “How effective is probiotic as an adjunct to nonsurgical therapy compared to nonsurgical therapy alone in the management of peri-implant disease in humans as measured by reduction in bleeding on probing, plaque accumulation, and probing pocket depth at implant (PPDI) level?”

Inclusion criteria

• Participants: Patients diagnosed with peri-implant disease (peri-implant mucositis or peri-implantitis)

• Intervention: Probiotics immediately started as an adjunct to nonsurgical therapy

• Comparison: Nonsurgical therapy alone or combined with a placebo

• Outcomes: Bleeding on probing, plaque index, and PPDI level with at least 4 weeks of re-evaluation

• Study design: Randomized controlled trial (RCT).

Exclusion criteria

• Duplicate studies

• Publications in languages other than English

• Studies with patients who had received local or systemic antibiotic or probiotic treatments within 3 months before study initiation

• Patients who received adjuncts other than probiotics along with standard nonsurgical therapy.

Search strategy

Electronic databases Medline (OVID), ScienceDdirect, and Cochrane Central Register of Controlled Trials were searched till June 30, 2021, for eligible articles. In addition, a hand searching was carried out in key periodontal and implant journals (Journal of Clinical Periodontology, Journal of Periodontology, Journal of periodontal research, Clinical Oral Implants Research; International Journal of Oral and Maxillofacial Implants, Clinical Implant Dentistry and Related Research) over the past 10 years. References of included articles and related review articles were included in hand-searching. Search words used in Medline included: [(Periimplantitis OR Peri-implant disease OR Peri implant * OR probing pocket depth) AND (Intervention OR Therapy OR Treatment) OR (Scaling and debridement OR nonsurgical therapy) AND (Probiotic OR Probiotic * OR Probiotic therapy OR Probiotic effect OR Probiotic treatment)]. Search strategy for other search engines are provided as supplementary information after references. Search results from all databases were combined and duplicates were removed.

SCREENING AND SELECTION OF PAPERS

Titles and abstracts of selected publications were screened by two blinded reviewers independently (AR and NBN) and after careful examination, those papers that satisfy the eligibility criteria alone were included in the study. For articles with insufficient information in the title and abstract, the full text was obtained to decide on their eligibility. The full text of the selected papers was reviewed independently for studies appearing to meet the inclusion criteria. Disagreements between the authors were resolved after discussion. Kappa statistic was used to assess the reviewer’s agreement.

Characteristics of included studies were prepared in PICOS format in a tabular format by one investigator (NBN) which was counterchecked by the other investigator (AR).

RISK OF BIAS IN INDIVIDUAL STUDIES

Each author independently evaluated the methodological quality of the included studies using version 2 of the cochrane risk-of-bias tool for randomized trials 2.[18] Disagreements were resolved after discussion. Each study was graded according to seven domains: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and other biases. Review authors’ judgments were categorized as “low risk” of bias, “high risk” of bias, or “unclear risk” of bias in each of the seven domains. The judgment about “low risk” of bias suggests a high quality of evidence. Insufficient reporting details lead to an “unclear risk” of bias. The overall risk of bias was determined as low when all domains reported low risk and high risk was assigned when at least one domain reported high risk or multiple domains with unclear bias. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.[19]

Search outcomes and evaluation

Bleeding on probing at implant (BOPI) level was the primary outcome measurement and plaque index at implant (PII) level and PPDI level were the secondary outcomes. Each parameter in each publication was assessed by one author (NBN) and confirmed by the other investigator (AR). Mean difference and 95% confidence interval (CI) were used to describe continuous data (PPDI), while risk difference with 95% CI were used to describe dichotomous data (BOPI and PII) (presence or absence of bleeding and plaque accumulation).[20] Study heterogeneity was assessed by using the Cochrane Q test and I² value. P value of Q statistic <0.1 and I² >40% indicate heterogeneity.[9] Fixed-effects model and random-effect model were appropriately selected based on the heterogeneity of included studies. Forest plots were generated to present the difference in outcomes, and funnel plots were to investigate the publication bias. Review Manager (RevMan) software, version 5.4 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used to carry out all statistical analyses.

RESULTS

Study selection

In the preliminary search, 516 relevant titles and abstracts were found. Among them, 506 were excluded after examining the title and abstract and duplication of data. The full text of the remaining 10 publications was carefully read and among them, only 4 articles that satisfy the inclusion criteria alone were included [reasons for exclusion are given in Table 1].[11,21-25] Finally, a total of four publications fulfilled the inclusion criteria[12,26-28] and among them two articles presented with outcomes of two different patient groups.[26,27] Thus, this systematic review and meta-analysis were prepared with data from 6 individual studies [Figure 1]. There was 90% agreement between reviewers at this stage and the value of kappa statistics reflected an almost perfect agreement (κ = 0.89).

Table 1.

Excluded clinical studies and the reason for exclusion

Publication	Reason for exclusion
Mongardini et al.[21]	PDT used along with mechanical therapy
Flichy-Fernández et al.[11]	Without nonsurgical mechanical therapy in two groups
Peña et al.[22]	Probiotic started 15 days after mechanical therapy
Tada et al.[23]	Azithromycin used
Lauritano et al.[24]	Data not provided properly
Ahmedbeyli et al.[25]	Not written in English

PDT – Photodynamic therapy

Figure 1.

Flowchart of the selection process. NST: Nonsurgical therapy. n – number of articles

Quality and risk of bias assessment of selected studies

Figure 2 presents the risk of bias of selected articles. The percentage of high risk of bias among the included studies was only 2.3%, 4.76% was unclear bias whereas the remaining presented with low risk of bias. The overall risk of bias was high for Hallstrom et al.[12] alone. Figure 3 depicts the quality of evidence as assessed by GRADE tool. Moderate certainty is observed for a reduction in percentage BOP after 1 month whereas and true effect is probably close to the estimated effect. For all the other comparisons, there is only low certainty, and the true effect might be markedly different from the estimated effect.

Figure 2.

Risk of bias graph and summary

Figure 3.

GRADE Table. GRADE: Grading of recommendations, assessment, development, and evaluation; MD – Mean difference; CI – Confidence Interval

Characteristics of included studies

Table 2 shows the PICOS characteristics of included studies. All the included studies were single-cantered, and outcomes were assessed for one implant/patient. A total of 196 patients are included in the analysis. Four out of 6 included studies utilized placebos[12,26,28] whereas blank control was used in 2 studies.[27] Nonsmokers were included in 4 studies, whereas a single study was carried out on smokers alone. Similarly, peri-implant mucositis was the population included in 4 studies and 2 studies were conducted in peri-implantitis patients. The adjunctive use of chlorhexidine was mentioned along with mechanical debridement in 2 of the included studies. Side effects of probiotic use were not reported by any of the patients included in 3 studies. Strong (pepper) mint flavor was mentioned by a single patient in both groups of study by Laleman et al.[28] Patients were instructed to consume probiotics for 3 weeks (twice daily), 30 days (once daily), and 3 months (twice daily) by Alqahtani et al.,[27] Galofre et al.[26] and Hallstrom et al.,[12] respectively. The number of probiotics or duration is not specified in one article (Laleman)[28]. Even though we have not restricted the probiotic agent, all the included studies utilized the same probiotic agent L. reuteri.

Table 2.

Evidence table of population intervention comparison outputs study characteristics of included studies

Author, year, country, title	Population of study	Study design and treatment groups	Treatment outcomes	Study findings
Galofre et al., (2017)[26] Spain, Clinical and microbiological evaluation of the effect of L. reuteri in the treatment of mucositis and peri-implantitis: A triple-blind randomized clinical trial	n (T/C)=22 (11/11) Age (T/C): 61.5±10.4/60.0±9.5 Sex (%) male/female (T/C): 73/27 and 55/45 Smoking status: Nonsmokers Disease status: PPDI ≥4 mm with BOPI and/or suppuration and no evidence of radiographic bone loss	Randomized, controlled, parallel-design, triple-blind prospective clinical study Test: Mechanical therapy with probiotic lozenge once a day for 30 days Control: Mechanical therapy with placebo lozenges	Primary outcome: PPDI reduction Secondary outcomes: Percentage reduction in BOPI and PII Other outcomes: Microbiological assessment Re-evaluation time points: After 1 and 3 months	A similar reduction in PPDI in both groups after 30 days, a significant reduction in the test group after 90 days No significant difference in plaque index between the groups. Significant reduction in BOPI in the test group Limited microbiological effects (reduction in P. gingivalis after 90 days) No side effects reported
Galofre et al., (2017)[26] Spain, Clinical and microbiological evaluation of the effect of L. reuteri in the treatment of mucositis and peri-implantitis: A triple-blind randomized clinical trial	n (T/C)=22 (11/11) Age: 61.7±7.0/56.8±9.3 Sex (%) male/female: 36/64 and 45/55 Smoking status: Nonsmokers Disease status: The presence of mucosal inflammation with BOPI and/or suppuration, probing pocket depth ≥5 mm and radiographic bone loss of ≥2 mm and/or ≥3 implant threads	Randomized, controlled, parallel-design, triple-blind prospective clinical study Test: Mechanical therapy with probiotic lozenge once a day for 30 days Control: Mechanical therapy with placebo lozenges	Primary outcome: PPDI reduction Secondary outcomes: Percentage reduction in BOPI and PII Other outcomes: Microbiological assessment Re-evaluation time points: After 1 and 3 months	Significant reduction in PPDI in the test group after 30 and 90 days No significant difference in plaque index between the groups Significant reduction in BOPI in the test group Limited microbiological effects No side effects reported
Hallstrom et al.,[12] (2016), Sweden, Probiotic supplements and debridement of peri-implant mucositis: A randomized controlled trial	n=49 (24/25) Age: 53.7±19.6 and 63.3±17.2 Sex (female/male): 17/7 and 14/11 Smoking status: 29% in the test and 8% in the placebo Disease status: One peri-implant site with probing depth ≥4 mm combined with bleeding and/or pus on probing	Double-blinded, parallel-design, randomized placebo-controlled trial Test: Topical application (sub- and supragingival with a ball-ended probe) of a droplet of oil containing L. reuteri strains around the selected implant, then lozenges containing the same bacteria twice a day for 3 months Control group: Placebo oil and lozenges	Primary outcome: PPDI Secondary outcomes: PII, BOPI, and presence of pus Other outcomes: Cytokines in GCF and microbial flora in plaque Timepoints: Baseline, 4, 12, and 26 weeks after baseline	No significant difference between groups in any of the outcomes No adverse effects
Alqahtani et al.,[27](2019), Saudi Arabia, Efficacy of MD with adjunctive probiotic therapy in the treatment of peri-implant mucositis in cigarette-smokers	n=40 (20 in each group) Age: 35.4±2.2 Sex: Only males were included Smoking status: All are smokers Disease status: Peri-implant BOPI and PPDI ≥3 mm at ≥30% sites and radiographic crestal bone loss up to 2 mm	Parallel design randomized clinical trial Test: Full-mouth MD using an ultrasonic scaler, twice daily CHX 0.12% for 2 weeks + probiotic lozenge of 2 L. reuteri strains twice a day for 3 weeks Control: All procedures in the test group except probiotic	Outcome: PII, BOPI and PPDI Timepoint: 3 months and 6 months	No statistically significant difference in peri-implant PII, BOPI and PPDI at all-time intervals among the test and control group Adverse effects not mentioned
Alqahtani et al.,[27] (2019), Saudi Arabia, Efficacy of MD with adjunctive probiotic therapy in the treatment of peri-implant mucositis in never-smokers	n=40 (20 in each group) Age: 36.1±0.8 Sex: Only males were included Smoking status: All are nonsmokers Disease status: Peri-implant BOPI and PPDI ≥3 mm at ≥30% sites and radiographic crestal bone loss of up to 2 mm	Parallel design randomized clinical trial Test: Probiotic lozenge of 2 L. reuteri strains twice a day for 3 weeks Control: All procedures in the test group except probiotic	Outcome: PII, BOPI, and PPDI Timepoint: 3 months and 6 months	A statistically significant difference in peri-implant PII, BOPI, and PPDI at 3 months intervals, but not statistically significant after 6 months Adverse effects not mentioned
Laleman et al.,[28](2019) The usage of lactobacilli probiotic in the nonsurgical therapy of peri-implantitis: A randomized pilot study	n=23 (11 and 12) Age: 64±11 years in test and 69±9 years in control Sex (female/male):4/5 and 6/4 Smoking status: All are nonsmokers Disease status: Mean PPDI of 6 mm and no >3 mm BL measured on intra-oral radiographs	A double-blind, randomized, placebo-controlled study Probiotic group: OHI+MD+topical probiotic drops+probiotic lozenges (containing 2 strains of L. reuteri) placebo group: OHI + MD + topical placebo drops+placebo lozenge	BOPI, SBI, PPDI, and PII at the implant level FMBS. FMPS and microbiological evaluation	No statistically significant intergroup differences for FMBS and BOPI, SBI, and PPDI after 12 and 24 weeks. Significant reduction in PII and FMPS only in the probiotic group No adverse effects except for dry mouth or a changed feeling in the oral cavity for 3 patients in the control group Patient in both groups mentioned strong (pepper) mint flavor No intra-nor intergroup differences were recorded regarding the microbiological counts of periodontal pathogens

T – Test; C – Control; PPDI – Probing pocket depth at implant level; BOPI – Bleeding on probing at implant level; PII – Plaque index at implant level; GCF – Gingival crevicular fluid; CHX – Chlorhexidine; BL – Bone loss; OHI – Oral hygiene instructions; MD – Mechanical debridement; SBI – Sulcus bleeding index; FMBS – Full mouth bleeding score; FMPS – Full mouth plaque score; P. gingivalis – Porphyromonas gingivalis; L. reuteri – Lactobacillus reuteri; n – number of samples

Results of meta-analysis

% reduction in bleeding on probing

Due to the heterogeneity of studies, a random effect model was selected. Meta-analysis showed 28% and 19% more reduction in BOPI in the probiotic group at 1 and 3 months respectively and the results were statistically significant (P < 0.05 and CI is not crossing 0) [Figure 4]. At 6 months of recall, only a 3% reduction in BOPI was noticed when analyzed with both random effect and fixed effect models and both were statistically insignificant too (P > 0.05 and CI crossing 0).

Figure 4.

Forest plot of Bleeding on probing. NST: Nonsurgical therapy; CI: Confidence Interval; df: Degree of freedom. tau² – tau-squared, chi² – chi-squared, I² – is a measure of heterogeneity in meta analysis, Z – z-statistics are significance tests for the weighted average effect size, P – probability value. P<0.05 is significant

Percentage reduction in plaque

Due to the heterogeneity of studies, a random effect model was selected. Meta-analysis showed 23%, 19%, and 18% more reduction in PII in the probiotic group at 1, 3, and 6 months, respectively, and the results were statistically significant for the first two re-evaluations (P < 0.05 and CI is not crossing 0) [Figure 5].

Figure 5.

Forest plot of Plaque accumulation. CI: Confidence Interval; df: Degree of freedom. tau² – tau-squared, chi² – chi-squared, I² – is a measure of heterogeneity in meta analysis, Z – z-statistics are significance tests for the weighted average effect size, P – probability value. P<0.05 is significant

Reduction in probing pocket depth

Due to the heterogeneity of studies, a random effect model was selected. Meta-analysis showed greater probing depth reduction in the probiotic group after 1, 3, and 6 months (0.08 mm, 0.2 mm, and 0.12 mm, respectively), however, it was not statistically significant in any of the comparisons (P > 0.05 and CI crossing 0) [Figure 6].

Figure 6.

Forest plot of Periodontal pocket depth. NST: Nonsurgical therapy; CI: Confidence Interval; df: Degree of freedom. tau² – tau-squared, chi² – chi-squared, I² – is a measure of heterogeneity in meta analysis, Z – z-statistics are significance tests for the weighted average effect size, P – probability value. P<0.05 is significant

DISCUSSION

In the present systematic review, we have evaluated the adjunctive use of probiotics and mechanical therapy in managing the peri-implant disease. Surprisingly, all the included studies used the same probiotic agent L. reuteri; thus, meaningful comparisons were possible. The meta-analysis was conducted to provide evidence for the short-term benefits of the use of probiotics in terms of reduction in BOPI (28% and 19%) as well as plaque accumulation (23% and 19%) at 1 and 3 months. Statistical analysis did not reveal any significant pocket depth reduction in any of the comparisons. Like our findings, L. reuteri was reported to be beneficial in reducing BOP (14.66%) in chronic periodontitis patients at 3 months as per a previously conducted meta-analysis.[9] They have also reported a tendency for overall pocket depth reduction and significant reduction was observed for moderate and deep pockets, but we could not observe a similar finding in our analysis.

BOPI, PPDI, and PII were the outcomes selected for the present analysis which are the important clinical indicators of peri-implant diseases. The significant reduction in BOPI and plaque indicates the advantage of probiotics in controlling clinical inflammation and etiological factors. Pocket depth reduction is also a desirable outcome to achieve pocket closure, especially in peri-implantitis cases. As per our analysis evidence is not strong to demonstrate the advantage of probiotics in reducing the pocket depth and future studies with more samples are needed to arrive at a proper conclusion. Some of the included studies evaluated additional parameters like pus discharge,[12] inflammatory markers like cytokines in gingival crevicular fluid,[12] and microbiological parameters.[26,28] However, due to the inadequate number of studies and disparity in the analytical methods, we could not perform statistical analysis for these parameters. Future studies may generate evidence on these surrogate outcomes.

A major limitation of our analysis was the inclusion of a limited number of studies. Another limitation was the heterogeneity of the studies in terms of the probiotic regime and smoking status. Frequency and duration of application of probiotics varied from 3 weeks to 3 months given either once daily or twice daily. But surprisingly, prolonging the probiotic administration to 3 months does not provide any added advantage in any of the parameters investigated. Most of the studies were conducted on nonsmokers whereas one single study included smokers alone.[27] More reduction in BOPI and plaque was noticed for once daily regime[26] whereas maximum pocket depth reduction was noticed in nonsmokers who consumed probiotics twice daily for 30 days.[27] These results indicate the need for future studies to arrive at a consensus regarding the frequency and duration of probiotic administration.

Based on the GRADE evidence table, there is low evidence for all the comparisons except BOPI after 1 month. Thus, the true effect may be substantially different from the observed effect and the quality of future studies need to be improved.

Four systematic reviews were published previously on the same topic[13-15,29] and three of them had conducted a meta-analysis. Two of them analyzed parameters of peri-implant mucositis patients alone[13,15] whereas Albaker[14], 2019 included peri-implant mucositis and peri-implantitis, but the statistical analysis was conducted separately. Statistically, significant improvement was not detected in any of the parameters (BOPI, PPDI, and PII) in the above-mentioned reports. However, we could find a significant reduction in BOPI and PII after 1 and 3 months which may be because of the difference in the methodology employed and the studies included in our analysis were also different. Four studies included by Gao et al.[13] were excluded from our analysis mainly due to differences in study designs to bring about a more meaningful comparison. In all the previously published meta-analyses re-evaluations for up to 3 months were performed whereas we analyzed for up to 6 months to evaluate the long-term effectiveness of the probiotic agents. However, we could not observe any significant improvement during the 6-month re-evaluation which indicates a lack of long-term benefits of probiotic administration. Another difference is that we have analyzed clinical parameters of peri-implant mucositis and peri-implantitis together as both are two stages of the same disease and clinical evaluation methods are similar in both conditions.

Nonsurgical therapy alone showed a pocket depth reduction of 0.57 mm, a 22.41% reduction in BOPI according to a recent systematic review.[30] They could not find any additional benefits for adjunctive use of chlorhexidine along with nonsurgical therapy in pocket depth reduction or attachment gain. Even though they have included other adjunctive agents like probiotics statistical analysis was not performed. Hence, the additional benefits offered by adjunctive agents of nonsurgical therapy in managing peri-implant disease need further investigation.

CONCLUSION

The results of the present meta-analysis support the short-term benefits of adjunctive use of probiotics for reducing gingival bleeding and plaque accumulation. However, moderate certainty was observed only for a reduction in bleeding on probing after 1-month re-evaluation. The heterogeneity of the included studies limits the generalizability of the results. Future well-controlled studies may provide adequate data for statistical analysis to generate more evidence on the topic.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

SUPPLEMENTARY FILE

Supplementary information: Search strategy employed for different search engines

Search terms used for MEDLINE, Cochrane Central Register of Controlled Trials, and Science Direct databases. The following strategy was used in the search using Boolean operators and an asterisk symbol (*) as truncation, which was employed to identify papers using MesH, keywords, and other free terms: ([(Periimplantitis OR Peri-implant disease OR Peri implant * OR probing peri-implant pocket depth) AND (Intervention OR Therapy OR Treatment)] OR [Scaling and root planning OR SRP OR nonsurgical therapy OR Periimplant treatment OR Periimplant therapy] AND [Probiotic OR Probiotic * OR Probiotic therapy OR Probiotic effect OR Probiotic treatment]) Only articles published in the English language have been considered.