Abstract
Objective:
This study conducted a bibliometric analysis to elucidate the research status, hotspots, and emerging trends regarding the application of probiotics in periodontal disease.
Methods:
Publications from 2005 to 2024 were retrieved from the Web of Science Core Collection, with search terms including “probiotics,” “periodontal disease,” “periodontitis,” and related synonyms. The complete records of the search results were exported in text format, and the collaboration networks and research hotspots were evaluated and visualized using VOSviewer and CiteSpace software.
Results:
A total of 378 publications were included, with Brazil contributing the largest share. Meanwhile, China has gradually increased its output in this field over the past 5 years. Collaboration levels among authors, institutions, and countries remain relatively low, suggesting room for greater synergy. Recent clinical trials evaluating the efficacy of probiotic interventions in the management of periodontitis have yielded promising therapeutic results. Probiotics may exert their effects in the treatment of periodontal disease through mechanisms such as antimicrobial activity, immune regulation, and enhancement of periodontal tissue barrier functions. However, these findings remain preliminary due to limitations in the studies, including small sample sizes and the lack of robust evidence from large-scale, multicenter clinical investigations. Keyword analysis revealed evolving research hotspots and emerging areas, such as new probiotic strains and new delivery methods.
Conclusion:
Research on probiotics in periodontal disease is expanding, yet the field is still nascent. Future efforts should focus on strengthening collaboration, conducting larger clinical studies, and elucidating underlying mechanisms to validate efficacy and optimize therapeutic applications.
Keywords: bibliometrics, periodontal disease, probiotic, visual analysis
1. Introduction
Periodontal diseases, encompassing both gingivitis and periodontitis, are the leading causes of tooth loss in adults worldwide.[1] Crucially, they represent a primary source of odontogenic infections, which cause significant oral morbidity.[2] Effective management of these infections is vital, as untreated periodontal disease not only leads to edentulism but also associates with serious systemic conditions like diabetes, adverse pregnancy outcomes, and cardiovascular disease.[3] The number of individuals affected by periodontal disease reached 1 billion in 2019, approximately double the number in 1999, making it the sixth most prevalent disease globally.[4] The prevalence and severity of periodontal disease in China are significantly high, indicating a prevalence of over 90% in adults, with data from the fourth National Oral Health Survey.[5] The frequency of periodontitis among different age groups was found to be 52.8% for those aged 35 to 44, 69.3% for those aged 55 to 64, and 64.6% for those aged 65 to 74. Severe periodontitis (stage III or IV) affected 10.6%, 37.3%, and 43.5% of these age groups, respectively.
The etiology of periodontal disease, specifically the debate between the nonspecific plaque hypothesis and the specific plaque hypothesis, has been a topic of contention for many years.[6] In recent years, there has been a gradual shift towards the theory of dysbiosis. This theory posits that periodontitis is not caused by the action of specific bacteria but by the disruption of the balance of oral flora, leading to immune dysregulation and resulting in local connective tissue destruction and alveolar bone resorption.[7]
Probiotics are defined as microorganisms that, at the right dose, are able to benefit the host.[8,9] They are beneficial for human health in several aspects, including antimicrobial activity, lactose intolerance management, diarrheal disease treatment, ulcer treatment, immunity stimulation, food preservation, and colon cancer prevention.[10] The gut microbiota is critically involved in the metabolic breakdown of complex dietary substrates, including polysaccharides, proteins, and other macronutrients. Furthermore, it contributes to host physiology through the biosynthesis of essential micronutrients, particularly vitamin K and B-complex vitamins, which are integral to energy homeostasis, erythropoiesis, and nucleic acid biosynthesis. In addition, microbial enzymatic activity, such as hydrolysis, modulates xenobiotic metabolism by transforming environmental toxicants and facilitates the regulation of intestinal mucus production.[11] Moreover, the application of probiotics is popular in the prevention and treatment of subgingival flora dysbiosis. For example, Lactiplantibacillus acidophilus, widely present in the human intestine, produces metabolites containing antibacterial components that can inhibit the growth of Porphyromonas gingivalis.[12] Most studies have focused on gram-positive bacteria, such as various classical Lactobacilli,[13,14] however, recently, gram-negative bacteria such as Akkermansia muciniphila have attracted attention as a new generation of probiotics.[15,16] Research into the role of probiotics in periodontal health has shown potential benefits, such as reducing inflammation,[17] modulating the balance between microbiota and the immune system,[18] restoring the epithelial barrier, and promoting bone regeneration.[19]
Despite the promising potential of probiotics in periodontal health, a comprehensive evaluation of the research output in this field is lacking. Bibliometrics, which utilizes mathematical and statistical methods to analyze scientific literature, provides an objective means to assess research trends and outcomes.[20] This study aims to fill this gap by offering a detailed overview of the current landscape of probiotic research in periodontal diseases, identifying key trends and research hotspots. By shedding light on these research hotspots, this analysis will serve as a valuable reference for researchers, guiding future investigations and contributing to the advancement of knowledge in the field of probiotics and periodontal health.
2. Materials and methods
The Medical Ethics Committee of the Hospital of Stomatology, Sun Yat-sen University waived ethical approval, as this study was a bibliometric analysis.
2.1. Databases
Bibliometric analysis was conducted using the Science Citation Index Expanded of the Web of Science (WoS), which is considered the optimal database for bibliometrics.[21]
2.2. Search terms
The search strategy is shown in Figure 1. Publications on DSC research were searched in WoS. The search method was as follows: TS=(“periodontitis” AND “prebiotics”) OR (“periodontitis” AND “probiotics”) OR (“periodontal disease” AND “prebiotics”) OR (“periodontal disease” AND “probiotics”) OR (“Lactobacillus” AND “periodontitis”) OR (“Lactobacillus” AND “periodontal disease”) OR (“Bifidobacterium” AND “periodontal disease”) OR (“Saccharomyces” AND “periodontal disease”) OR (“Enterococcus” AND “periodontal disease”) OR (“Gingivitis” AND “probiotics”) OR (“Gingivitis” AND “prebiotics”) OR (“peri-implantitis” AND “prebiotics”) OR (“peri-implantitis” AND “probiotics”) OR (“periodontal” AND “probiotics”). The publication dates were from January 1, 2005 to April 17, 2024. The publication type was set to article only. All records of each publication, including title, year of publication, authors’ names, nationality, affiliation, publication journal name, keywords, and abstract, were downloaded from the WoS database in the form of a TXT file. To avoid the impact of WoS database updates, all data searches and data downloads were performed on April 17, 2024.
Figure 1.
Literature search strategy for research on the use of probiotics in periodontal disease. A total of 821 articles were retrieved using keyword searches, and through manual screening, 378 articles that met the thematic criteria were identified.
Literature screening is a crucial step in research to ensure that only relevant works are included in the analysis.[22] In the case of selecting literature on the application of probiotics in periodontal diseases from a pool of 821 articles, a manual screening process was implemented. This meticulous second phase lasted approximately 2 weeks and led to the identification of 378 articles that closely aligned with the research topic. The entire screening process is illustrated in Figure 1.
2.3. Data standardization
The raw data extracted from scientific databases often contain multiple expressions of the same term, and not addressing these synonymous expressions could affect research results in bibliometric analysis.[23] Therefore, before analyzing the selected literature, a data disambiguation process is necessary to standardize the data.[24]
2.4. Data elements and collection method for bibliometric analysis
The metric analyses encompassed several variables, including “keywords,” “authors,” “year of publication,” “journal,” and “corresponding author’s affiliation country.” VOSviewer (version 1.6.15; Centre for Science and Technology Studies [CWTS], Leiden University, Leiden, the Netherlands), Excel (version 2406 Build 16.0.17726.20078), and Scimago Graphica (version 1.0.43; Scimago Lab, Spain) were used to analyze the coauthorship, co-occurrence, established coauthorship network visualization map, and keyword network visualization map.
3. Results
3.1. Amount and publishing trends of global publications
Between 2005 and April 16, 2024, a total of 378 articles were included according to the screening criteria depicted in Figure 2A. The application of probiotics in periodontal diseases showed slow growth in research output from 2005 to 2020, followed by a rapid increase in publications in this area after 2020.
Figure 2.
Publication trends and distribution in research on the use of probiotics in periodontitis. (A) Annual distribution of publications. (The bibliometric analysis captured 10 publications indexed as of the search termination date [April 16, 2024], representing an incomplete annual count for 2024.) It can be noted that the number of publications is increasing every year. (B) Number of articles published by different countries between 2005 and 2019. It can be observed that the countries with higher publication volumes in the early stages include Brazil and Japan. (C) Number of articles published by different countries between 2020 and 2024. It can be noted that in China, the number of publications in this area has increased significantly over the past 5 years.
3.2. High-yield journals
Most articles on the use of probiotics for the treatment of periodontitis are published in 2 main categories: Periodontology and Microbiology. The Journal of Clinical Periodontology has published the largest number of studies (impact factor [IF] = 5.8, 24 articles), followed by the Journal of Periodontology (IF = 4.2, 20 articles) and Clinical Oral Investigations (IF = 3.1, 13 articles). The top 10 journals are listed in Table 1.
Table 1.
Top 10 journals with the most published articles.
| Rank | Journal | IF (2024) | Documents | Citations |
|---|---|---|---|---|
| 1 | Journal of Clinical Periodontology | 5.8 | 24 | 1617 |
| 2 | Journal of Periodontology | 4.2 | 20 | 617 |
| 3 | Clinical Oral Investigations | 3.1 | 13 | 277 |
| 4 | Archives of Oral Biology | 2.2 | 12 | 260 |
| 5 | Journal of Periodontal Research | 3.4 | 12 | 382 |
| 6 | Microorganisms | 4.1 | 11 | 207 |
| 7 | Beneficial Microbes | 3.0 | 10 | 178 |
| 8 | Oral Diseases | 2.9 | 10 | 438 |
| 9 | Probiotics and Antimicrobial Proteins | 4.4 | 10 | 185 |
| 10 | Nutrients | 4.8 | 9 | 93 |
3.3. Contribution of countries/regions and international cooperation
Among the countries/regions that have contributed to this field (Table 2), Brazil has published the most relevant articles (57 publications), followed by China (51) and Italy (39). The United States emerged as the most cited country (1372 citations), followed by Italy (1224) and Brazil (1199).
Table 2.
Top 10 countries with the most published articles.
| Rank | Country | Documents | Citations |
|---|---|---|---|
| 1 | Brazil | 57 | 1199 |
| 2 | China | 51 | 496 |
| 3 | Italy | 39 | 1224 |
| 4 | USA | 37 | 1372 |
| 5 | Japan | 30 | 917 |
| 6 | South Korea | 28 | 429 |
| 7 | Spain | 18 | 636 |
| 8 | India | 17 | 221 |
| 9 | Belgium | 16 | 748 |
| 10 | England | 15 | 612 |
Using VOSviewer, coauthorship clustering analysis was conducted on 28 countries with more than 5 articles published (Slovenia was excluded due to lack of collaboration with other countries). The analysis revealed 5 clusters, as depicted in Figure 3. The first cluster includes Canada, Chile, France, Iran, Norway, Pakistan, Saudi Arabia, and Thailand. The second cluster consists of Brazil, Denmark, Germany, Spain, Sweden, and Switzerland. The third cluster includes Australia, India, Japan, Malaysia, and China. The fourth cluster comprises Belgium, Finland, South Korea, Turkey, and the USA. The fifth cluster includes England, Italy, Poland, and Portugal.
Figure 3.
Cluster maps of the countries/regions. In the graph, the nodes represent countries, the size of the nodes represents the number of documents sent, the connecting lines represent the cooperation between countries, and the thickness of the connecting lines represents the amount of cooperation. It has been noted that international collaboration is not sufficiently strong. The top countries in terms of the number of articles published were China, Brazil, Italy, and the United States.
3.4. Contribution of institutions
The organization output chart lists the top 10 institutions that contributed the most (Table 3). The University of São Paulo published the most articles (33), Sichuan University ranked second (11), and the State University of Campinas tied for third (7).
Table 3.
Top 10 institutions with the most published articles.
| Rank | Institution | Country | Documents | Citations |
|---|---|---|---|---|
| 1 | University of São Paulo | Brazil | 33 | 816 |
| 2 | Sichuan University | China | 11 | 195 |
| 3 | State University of Campinas | Brazil | 7 | 278 |
| 4 | University Hospitals Leuven | Belgium | 7 | 241 |
| 5 | Sao Paulo State University | Brazil | 7 | 196 |
| 6 | University of Milan | Italy | 6 | 68 |
| 7 | Karolinska Institute | Sweden | 6 | 331 |
| 8 | University of Copenhagen | Denmark | 6 | 504 |
| 9 | University of Turku | Finland | 6 | 195 |
| 10 | São Paulo State University (UNESP) | Brazil | 6 | 93 |
3.5. Contribution of authors
The top 10 authors published 80 articles, accounting for 21.2% of all articles (Table 4). In the last 20 years of research on the use of probiotics in periodontitis, the 5 authors who published the most articles were Messora Michel R. (14 articles), Furlaneto Flavia A. C. (11 articles), Ervolino Edilson (10 articles), Salvador Sergio L. (9 articles), and Salvador Sergio L. (8 articles). The 5 most cited authors are Messora Michel R. (480 citations), Furlaneto Flavia A. C. (419 citations), Salvador Sergio L. (307 citations), Ervolino Edilson (234 citations), and Silva Pedro H. F. (215 citations). The total number of authors with more than 3 publications is 87, and the coauthor network they form is shown in Figure 4.
Table 4.
The top 10 authors with the most published articles.
| Rank | Author | Documents | Citations | Average citation per paper |
|---|---|---|---|---|
| 1 | Messora Michel R. | 14 | 480 | 34.3 |
| 2 | Furlaneto Flavia A. C. | 11 | 419 | 38.1 |
| 3 | Ervolino Edilson | 10 | 234 | 23.4 |
| 4 | Salvador Sergio L. | 9 | 307 | 34.1 |
| 5 | Silva Pedro H. F. | 8 | 215 | 26.9 |
| 6 | Mayer Marcia P. A. | 7 | 83 | 11.9 |
| 7 | Ishikawa Karin H. | 6 | 78 | 13.0 |
| 8 | Alves Mayer Marcia Pinto | 5 | 172 | 34.4 |
| 9 | Casarin Renato | 5 | 203 | 40.6 |
| 10 | Messora Michel Reis | 5 | 52 | 10.4 |
Figure 4.
Cluster maps of the authors. The nodes in the graph represent the size of the author nodes represent the number of posts made by the authors, and the connecting lines represent the collaboration between the authors, and the distance and the thickness of the link between nodes show the relative strength of the relation. It was noted that although some authors collaborated with each other, there was a lack of extensive academic collaboration within the research community.
3.6. Top 10 highly cited articles
According to the VOSviewer analysis, the top 10 cited articles are presented in Table 5. The most cited article is “Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri” published by Krasse et al in 2006, ranking first. The second most cited article is “Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study” published by Teughels et al in 2013, ranking second. The third most cited article is “Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity” published by Koll-Klais et al in 2005, ranking third. Four out of the top 10 cited articles were published in the Journal of Clinical Periodontology, indicating that this journal is of high quality in this field.
Table 5.
Top 10 high-cited articles.
| Rank | Title | Author | Year | Journal | Citations | Main discoveries |
|---|---|---|---|---|---|---|
| 1 | Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri | Krasse P., Carlsson B., Dahl C., Paulsson A., Nilsson A., Sinkiewicz G. | 2006 | Swedish Dental Journal | 206 | After 14 days of using chewing gum containing Lactobacillus reuteri, patients with gingivitis exhibited a significant reduction in both the gingival index and plaque index compared to the placebo group. |
| 2 | Clinical and microbiological effects of Lactobacillus reuteri probiotics in the treatment of chronic periodontitis: a randomized placebo-controlled study | Teughels W., Durukan A., Ozcelik O., Pauwels M., Quirynen M., Haytac M. C. | 2013 | Journal of Clinical Periodontology | 194 | In patients with periodontitis, the group that received SRP combined with probiotics demonstrated more significant reductions in pocket depth, decreased loss of attachment, and a greater reduction in periodontal pathogens belonging to the genus Prevotella compared to the control group. |
| 3 | Oral lactobacilli in chronic periodontitis and periodontal health: species composition and antimicrobial activity | Koll-Klais P., Mändar R., Leibur E., Marcotte H., Hammarström L., Mikelsaar M. | 2005 | Oral Microbiology and Immunology | 184 | Compared to patients with chronic periodontitis, homofermentative Lactobacillus species are more prevalent among periodontally healthy individuals. Both homofermentative and heterofermentative Lactobacillus in the oral cavity demonstrate antimicrobial activity against periodontal pathogens such as Streptococcus mutans and Actinobacillus actinomycetemcomitans. |
| 4 | Probiotics: contributions to oral health | Meurman J. H., Stamatova I. | 2007 | Oral Diseases | 179 | This review encompasses the mechanisms of bacterial adhesion, the potential for probiotics to colonize the oral cavity, interspecies interactions, and the possible immunoregulatory effects. |
| 5 | Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid | Twetman S., Derawi B., Keller M., Ekstrand K., Yucel-Lindberg T., Stecksen-Blicks C. | 2009 | Journal of Clinical Periodontology | 167 | In patients with mild to moderate gingivitis, the levels of the inflammatory cytokines TNF-α and IL-8 significantly decreased following the consumption of chewing gum containing Lactobacillus reuteri, while IL-1β showed a nonsignificant decreasing trend. |
| 6 | Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy | Hajishengallis G., Chavakis T., Lambris J. D. | 2020 | Periodontology 2000 | 166 | Probiotics may improve the clinical symptoms of periodontal diseases by modulating the oral microbiota and the host immune response. |
| 7 | Probiotics for managing caries and periodontitis: systematic review and meta-analysis | Gruner D., Paris S., Schwendicke F. | 2016 | Journal of Dentistry | 160 | Probiotics significantly improved gingival health by reducing probing bleeding and the gingival index, as well as markedly decreasing probing pocket depth. |
| 8 | The oralome and its dysbiosis: new insights into oral microbiome-host interactions | Radaic A., Kapila Y. L. | 2021 | Computational and Structural Biotechnology Journal | 153 | Probiotics not only secrete substances such as H2O2 to inhibit the growth of anaerobic bacteria, but they also help regulate the balance of the oral microbiota, thereby preventing periodontal disease. Additionally, they can exert their effects by suppressing the biofilm formation and adhesion of pathogenic bacteria. |
| 9 | Improvement of periodontal condition by probiotics with Lactobacillus salivarius WB21: a randomized double-blind placebo-controlled study | Shimauchi H., Mayanagi G., Nakaya S., Minamibuchi M., Ito Y., Yamaki K., Hirata H. | 2008 | Journal of Clinical Periodontology | 149 | Lactobacillus salivarius WB21 can improve the plaque index and probing pocket depth, with more pronounced effects observed in smokers, who also exhibited a significant reduction in salivary lactoferrin levels. |
| 10 | Clinical and microbiological effects of probiotic lozenges in the treatment of chronic periodontitis: a 1-year follow-up study | Tekce M., Ince G., Gursoy H., Ipci S. D., Cakar G., Kadir T., Yilmaz S. | 2015 | Journal of Clinical Periodontology | 131 | The use of throat lozenges containing Lactobacillus reuteri as an adjunctive treatment to SRP resulted in significantly lower plaque index, gingival index, probing bleeding, and probing depth in patients over the course of 1 year. Lozenges containing Lactobacillus reuteri also contribute to the attenuation of the recolonization of periodontal pathogens. |
SRP = scaling and root planning.
3.7. Keyword analysis
Through VOSviewer analysis of 378 articles, 82 keywords appearing at least 10 times were identified and categorized into 4 clusters, as depicted in Figure 5. The first cluster (red) consists of 21 keywords, with prominent terms including “periodontal disease,” “Porphyromonas gingivalis,” “health,” “biofilm,” and “Streptococcus mutans.” The second cluster (blue) comprises 20 keywords, with notable terms such as “double-blind,” “Lactobacillus,” “oral health,” “dental caries,” and “caries.” The third cluster (green) contains 21 keywords, with prominent terms including “probiotics,” “periodontitis,” “disease,” “bacteria,” and “inflammation.” The fourth cluster (yellow) encompasses 20 keywords, with notable terms such as “Lactobacillus reuteri,” “gingivitis,” “chronic periodontitis,” “lozenges,” and “efficacy.”
Figure 5.
Keyword co-occurrence graph. The size of the dots represents the number of occurrences of the corresponding keywords, and the connecting lines represent the strength of the association between the keywords. It can be noted that these keywords have been clustered into 4 major categories, each indicated by red, blue, green, and yellow labels.
The keywords were further analyzed using CiteSpace to identify those with the strongest citation bursts and to create a time zone map of the keywords, as shown in Figure 6. Keywords with a sudden increase in occurrence from 2007 to 2024 include “Lactobacillus rhamnosus GG,” “crevicular fluid,” “salivary mutans streptococci,” “Actinobacillus actinomycetemcomitans,” “chewing gums,” “microbiota,” “chronic periodontitis,” “subgingival,” and “association.” The time zone map reveals that earlier appearing keywords include “Porphyromonas gingivalis,” “periodontal disease,” “chronic periodontitis,” “Lactobacillus reuteri,” and “health.” More recent keywords include “efficacy,” “oral microbiome,” “model,” and “gene expression.”
Figure 6.
Keyword hotspot evolution graph. (A) Top 9 keywords with the strongest citation bursts. (B) The time zone map of the keywords. The size of the dots represents the number of occurrences of the corresponding keywords, and the connecting lines represent the strength of the association between the keywords. It can be observed that earlier appearing keywords include “Porphyromonas gingivalis,” “periodontal disease,” “chronic periodontitis,” “Lactobacillus reuteri,” and “health.” More recent keywords include “efficacy,” “oral microbiome,” “model,” and “gene expression.” It is evident that, as research advanced, greater emphasis was placed on more in-depth issues, such as the mechanisms by which probiotics influence the pathogenesis of periodontitis.
4. Discussion
Bibliometrics and visualization analysis can reflect the current research status and predict future research trends. This study utilized bibliometrics and visualization analysis to investigate the current research on probiotics in periodontal disease from aspects such as authors, journals, countries, and keywords. We found that the number of relevant articles published has increased rapidly in the past 5 years, indicating a continuing upward trend.
The number of annual publications in the field has been gradually increasing. Quantitative analysis reveals a biphasic growth pattern: a modest increase in publications during 2005 to 2015 (average annual growth rate = 17.5%), succeeded by exponential growth after 2015 (CAGR = 28.2%), mirroring the prototypical development curve of nascent scientific fields. The initial publications primarily focused on fundamental research, with the first publication dating back to 2005. Clinical trials exploring the use of probiotics in periodontal diseases began relatively early, in 2006, due to the earlier application of probiotics in treating enteritis, which shares mechanistic similarities with periodontitis related to dysbiosis. From 2005 to 2019, research output in this area grew slowly, but there was a notable surge in publications after 2020. This surge can largely be attributed to the significant increase in the number of papers published by Chinese researchers. As shown in Figure 2, China ranked eighth with 9 papers in the 15 years leading up to 2020 (Fig. 2B). However, in the 5 years following 2020, China rose to the top position with 42 publications (Fig. 2C). This significant increase is largely attributed to the growing interest and commitment of Chinese scholars to this field. A pronounced shift in geographical research dominance is evident, with developing countries contributing a substantially higher proportion of total publications in recent years. This transition is largely attributable to accelerated research output from China and Brazil. Notably, Brazil has maintained consistent leadership in publication volume since the early stages of the field’s development, suggesting the presence of a distinctive academic ecosystem that fosters sustained scholarly productivity.
In the most highly cited article by Krasse et al, a double-blind, randomized, placebo-controlled trial demonstrated that Lactobacillus reuteri effectively reduces the Gingival Index (33.1%) and Plaque Index (9%) in patients with moderate to severe gingivitis.[25] Other studies have also evaluated different probiotics and treatment methods through parameters such as periodontal pocket depth and attachment loss, revealing that probiotics have a significant therapeutic effect on periodontal diseases. In summary, the most frequently cited articles predominantly focus on clinical trials and the analysis of clinical samples, while research exploring the deeper mechanisms underlying the antimicrobial and anti-inflammatory actions of probiotics has received insufficient attention.
According to the keyword co-occurrence network depicted in Figure 5, this visualization reveals contemporary research focus on the relationship between periodontal pathogens, probiotic interventions, and clinical outcomes. The red cluster highlights the strong association between periodontal pathogens, biofilm formation, and the pathogenesis of periodontal diseases. In contrast, the green cluster demonstrates the protective effects of probiotics on periodontal tissues. The yellow cluster reflects scholars’ ongoing efforts to standardize the evaluation criteria for probiotic efficacy in periodontal therapy. These findings collectively indicate that current probiotic applications in periodontal disease management require more evidence-based clinical guidelines to establish standardized protocols.
From Figure 6, the keywords with the strongest citation bursts and the time zone map of the keywords show that new research hotspots continue to emerge. The research hotspots have evolved from early studies focusing solely on the relationship between probiotics, periodontal disease, and periodontal pathogens to more in-depth investigations into treatment mechanisms, treatment outcomes, and connections with other diseases. In the early stages, basic research tended to focus on common immunoregulatory mechanisms and the antimicrobial peptides produced by probiotics.[26] Later, researchers recognized that studying the use of probiotics in treating periodontal diseases involves a comprehensive approach that includes antimicrobial activity, microbial enzymatic activity, such as hydrolysis,[11] regulation of dysbiosis, immunoregulation, host physiology,[11] bone metabolism modulation, and oxidative stress effects.[27] This multidimensional synergy deepened the investigation into probiotics across various signaling pathways and the therapeutic effects of novel probiotics on periodontal diseases.[28] Initially, clinical trials leaned toward the use of commonly available probiotics for the treatment of periodontal diseases or exploring various probiotic delivery methods such as toothpaste and chewing gums.[29] Over time, clinical trials increasingly focused on using probiotics as adjunctive therapy alongside other treatment modalities for periodontitis, peri-implantitis, and periodontal diseases associated with systemic conditions.
From Table 2, it is evident that although Brazil and China have a high volume of publications in this field, their citation counts are low. In contrast, the United States and Italy, despite having fewer publications, have higher citation counts, indicating greater research recognition. The top contributors to scientific publications are researchers from Brazil, who focus primarily on the effects of Bifidobacterium animalis subsp. lactis and Bacillus subtilis on periodontitis,[30] peri-implantitis,[31] gingivitis,[32] and other periodontal diseases. Their work involves clinical double-blind randomized controlled trials and animal experiments to investigate the clinical effects and underlying mechanisms of these 2 probiotics. The main journals they published in are the Journal of Periodontology and the Journal of Clinical Periodontology. Highly cited articles in this field, mostly authored by researchers from the United States and Italy and published in journals such as Periodontology 2000, are review articles summarizing the mechanisms of probiotic protection of periodontal tissues, providing insights into the prospects of probiotics in periodontal health. These reviews emphasize the potential benefits of probiotics in maintaining oral health, managing periodontal diseases, and serving as alternative antimicrobial therapies.[27]
We identified a total of 15 research groups, with the 2 most prolific and collaborative groups (red and green) being the Oral & Maxillofacial Surgery & Periodontology Department and the Oral Microbiome Laboratory of the Biomedical Sciences Institute at the University of São Paulo in Brazil. These 2 groups have jointly published numerous articles on the use of Bifidobacterium animalis subsp. lactis and Bacillus subtilis for treating periodontitis, peri-implantitis, gingivitis, and other periodontal diseases. Due to the close connection between periodontology and microbiology research, these groups complement each other effectively. However, overall inter-group collaborations remain limited. In the future, other research groups should follow the example of these Brazilian teams by increasing interdisciplinary and international exchanges and interactions, thereby promoting multicenter and multidisciplinary research efforts.
Although research on the potential of probiotics in the treatment of periodontitis has made strides, there are still some limitations in current studies. There is insufficient understanding of the mechanisms of probiotic therapy for periodontitis, and further research is needed to delve deeper into the mechanisms of probiotic action in the oral environment. Clinical trials of probiotic treatment for periodontitis are currently small in scale, lacking extensive, multicenter clinical trial data support. The long-term effectiveness of probiotics in preventing and treating periodontal diseases still needs further evaluation. The mode of drug delivery for probiotics in the treatment of periodontal diseases needs improvement. Current drug delivery methods often lead to difficulties in maintaining effective concentrations of probiotics at periodontal disease sites over extended periods, thereby diminishing their long-term efficacy. In addition, these probiotics frequently migrate to other nontarget organs, such as the gastrointestinal tract.[33] The development of innovative materials such as hydrogels, microspheres, and electrospun fibers presents new opportunities for drug delivery systems. These advanced systems are expected to enhance the concentration of probiotics specifically targeted to the teeth and periodontal pockets, thereby reducing the potential risk of their unintended entry into other organs.[34] In the future, broader, multicenter clinical trials should be conducted to substantiate the effectiveness and safety of probiotic treatment for periodontitis, thereby offering more robust evidence for its clinical application. Further exploration of the mechanisms of probiotic action in the oral environment, including their interaction with the oral microbiome and their impact on immune regulation, is warranted. Strengthening collaboration across multiple disciplines such as oral medicine, microbiology, immunology, and materials science can propel research and clinical applications of probiotic treatment for periodontitis.
Although this investigation systematically analyzed English-language literature using the Web of Science database, the selected keywords may not comprehensively encompass the research domain’s breadth given its extensive scope. Furthermore, recently published articles likely exhibit underrepresentation due to inherently constrained citation metrics from shorter publication horizons. Future research should address these limitations through expanded keyword taxonomies with multi-database validation, employing time-normalized citation analysis (e.g., Bounded Citation Window) to mitigate recency bias.
5. Conclusions
This research contributes significantly to the understanding of probiotic therapy for periodontal diseases through comprehensive and objective bibliometric and visualization analyses. This study offers comprehensive insights into the structure, dynamics, and trends of scientific research, which are essential for mapping the research landscape, guiding strategic decisions, and fostering collaboration and innovation in the field of probiotics and periodontal disease research. Although there has been some progress in investigating the role of probiotics in periodontal disease, the overall number of studies remains limited, and further research is needed to explore treatment options, efficacy, and the specific immunological and microbiological mechanisms involved.
Author contributions
Conceptualization: Qizhe Zheng, Fei Liu, Panpan Wang.
Data curation: Qizhe Zheng, Yuwei Gao, Fei Liu, Panpan Wang.
Formal analysis: Qizhe Zheng, YunShuang Hu, Panpan Wang.
Investigation: Qizhe Zheng, Yuwei Gao, Yinglin Chu, YunShuang Hu.
Methodology: Qizhe Zheng, Yuwei Gao, YunShuang Hu.
Software: Qizhe Zheng, Yuwei Gao, Yinglin Chu, YunShuang Hu.
Supervision: Botao Gao, Panpan Wang.
Validation: Botao Gao, Fei Liu, Panpan Wang.
Visualization: Botao Gao, Fei Liu, Panpan Wang.
Project administration: Fei Liu, Panpan Wang.
Resources: Fei Liu, Panpan Wang.
Funding acquisition: Panpan Wang.
Writing – original draft: Qizhe Zheng, Yinglin Chu.
Writing – review & editing: Botao Gao, Fei Liu, Panpan Wang.
Abbreviations:
- IF
- impact factor
- WoS
- Web of Science
This work was supported by grants from the Natural Science Foundation of Guangdong Province China (2025A1515012643 and 2016A030310214 to PW), the National Natural Science Foundation of China (81500871 to PW), the Henan Provincial Medical Science and Technology Research Project (SBGJ202502070 to FL), and the Henan Provincial Department of Education Key Scientific Research Project of Higher Education Institutions (26A320052 to FL).
The Medical Ethics Committee of Hospital of Stomatology, Sun Yat-sen University waived ethical approval, as this study was a bibliometric analysis.
The authors have no conflicts of interest to declare.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Zheng Q, Gao Y, Chu Y, Hu Y, Gao B, Liu F, Wang P. Probiotic research in periodontal disease: Insights from bibliometric and visualization analysis. Medicine 2026;105:37(e50521).
BG, FL, and PW contributed to this article equally.
Contributor Information
Qizhe Zheng, Email: periopanda@163.com.
Yuwei Gao, Email: 8592436@qq.com.
Yinglin Chu, Email: perioguipei@163.com.
YunShuang Hu, Email: wpp0725@163.com.
Botao Gao, Email: 8592436@qq.com.
Fei Liu, Email: luiwang2008@163.com.
References
- [1].Kaur G, Mohindra K, Singla S. Autoimmunity—basics and link with periodontal disease. Autoimmun Rev. 2017;16:64–71. [DOI] [PubMed] [Google Scholar]
- [2].Dipalma G, Laforgia A, Ciccarese D, et al. Odontogenic infections: updated recommendations and best practices. Int J Infect. 2024;8:3–13. [Google Scholar]
- [3].Lei S, Li J, Yu J, et al. Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway. Int J Oral Sci. 2023;15:3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Zhang X, Wang X, Wu J, et al. The global burden of periodontal diseases in 204 countries and territories from 1990 to 2019. Oral Dis. 2022;30:754–68. [DOI] [PubMed] [Google Scholar]
- [5].Jiao J, Jing W, Si Y, et al. The prevalence and severity of periodontal disease in Mainland China: data from the Fourth National Oral Health Survey (2015–2016). J Clin Periodontol. 2020;48:168–79. [DOI] [PubMed] [Google Scholar]
- [6].Dong Q, Chen H, Peng S, et al. Oral microbial community assembly under the influence of periodontitis. PLoS One. 2017;12:e0182259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Meuric V, Gall-David S Le, Boyer E, et al. Signature of microbial dysbiosis in periodontitis. Appl Environ Microbiol. 2017;83:e00462-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Depoorter L, Vandenplas Y. Probiotics in pediatrics. A review and practical guide. Nutrients. 2021;13:2176. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].You S, Ma Y, Yan B, et al. The promotion mechanism of prebiotics for probiotics: a review. Front Nutr. 2022;9:1000517. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Masood MI, Qadir MI, Shirazi JH, Khan IU. Beneficial effects of lactic acid bacteria on human beings. Crit Rev Microbiol. 2011;37:91–8. [DOI] [PubMed] [Google Scholar]
- [11].Simon Yu MDE, Festa F, Muralidhar P. The immunological role of microbiota in the human intestine and the bidirectional communication of the gut-brain axis. Int J Infect. 2024;8:20–3. [Google Scholar]
- [12].Ma L, Li F, Zhang X, Feng X. Biochemical characterization of a recombinant Lactobacillus acidophilus strain expressing exogenous FomA protein. Arch Oral Biol. 2018;92:25–31. [DOI] [PubMed] [Google Scholar]
- [13].Zhao JJ, Feng XP, Zhang XL, Le KY. Effect of Porphyromonas gingivalis and Lactobacillus acidophilus on secretion of IL1B, IL6, and IL8 by gingival epithelial cells. Inflammation. 2012;35:1330–7. [DOI] [PubMed] [Google Scholar]
- [14].Reid G, Gadir AA, Dhir R. Probiotics: reiterating what they are and what they are not. Front Microbiol. 2019;10:424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Si J, Kang H, You HJ, Ko G. Revisiting the role of Akkermansia muciniphila as a therapeutic bacterium. Gut Microbes. 2022;14:2078619. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol. 2004;54:1469–76. [DOI] [PubMed] [Google Scholar]
- [17].Yang B, Pang X, Li Z, Chen Z, Wang Y. Immunomodulation in the treatment of periodontitis: progress and perspectives. Front Immunol. 2021;12:781378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Yu S, Emidio M D, Festa F, Muralidhar P. The immunological role of microbiota in the human intestine and the bidirectional communication of the gut-brain axis. Int J Infect. 2024;8:20–3. [Google Scholar]
- [19].Han NN, Jia L, Guo LJ, et al. Balanced oral pathogenic bacteria and probiotics promoted wound healing via maintaining mesenchymal stem cell homeostasis. Stem Cell Res Ther. 2020;11:12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Durieux V, Gevenois PA. Bibliometric indicators: quality measurements of scientific publication. Radiology. 2010;255:342–51. [DOI] [PubMed] [Google Scholar]
- [21].Pranckutė R. Web of Science (WoS) and scopus: the titans of bibliographic information in today’s academic world. Publications. 2021;9:12. [Google Scholar]
- [22].Zhao H, Liu JB, Bao ZF, Xu YX, Wang ZQ. Global research trends in dental stem cells: a bibliometric and visualized study. Tissue Eng Part B Rev. 2022;28:733–44. [DOI] [PubMed] [Google Scholar]
- [23].Moral-Muñoz JA, Herrera-Viedma E, Santisteban-Espejo A, Cobo MJ. Software tools for conducting bibliometric analysis in science: an up-to-date review. El Profesional de la Información. 2020;29:1. [Google Scholar]
- [24].Wang C, Chen X, Yu T, Liu Y, Jing Y. Education reform and change driven by digital technology: a bibliometric study from a global perspective. Human Social Sci Commun. 2024;11:256. [Google Scholar]
- [25].Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri. Swed Dent J. 2006;30:55–60. [PubMed] [Google Scholar]
- [26].Meurman JH, Stamatova I. Probiotics: contributions to oral health. Oral Dis. 2007;13:443–51. [DOI] [PubMed] [Google Scholar]
- [27].Nguyen T, Brody H, Radaic A, Kapila Y. Probiotics for periodontal health-Current molecular findings. Periodontology 2000. 2021;87:254–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [28].Zhang JY, Duan Z. Identification of a new probiotic strain, Lactiplantibacillus plantarum VHProbi® V38, and its use as an oral health agent. Front Microbiol. 2022;13:10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Twetman S, Derawi B, Keller M, Ekstrand K, Yucel-Lindberg T, Stecksen-Blicks C. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand. 2009;67:19–24. [DOI] [PubMed] [Google Scholar]
- [30].Messora MR, Pereira LJ, Foureaux R, et al. Favourable effects of Bacillus subtilis and Bacillus licheniformis on experimental periodontitis in rats. Arch Oral Biol. 2016;66:108–19. [DOI] [PubMed] [Google Scholar]
- [31].Santana SI, Silva PHF, Salvador SL, Casarin RCV, Furlaneto FAC, Messora MR. Adjuvant use of multispecies probiotic in the treatment of peri-implant mucositis: a randomized controlled trial. J Clin Periodontol. 2022;49:828–39. [DOI] [PubMed] [Google Scholar]
- [32].Levi Y, Ribeiro MC, Silva PHF, et al. Effects of oral administration of Bifidobacterium animalis subsp. lactis HN019 on the treatment of plaque-induced generalized gingivitis. Clin Oral Investig. 2023;27:387–98. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [33].Teughels W, Van Essche M, Sliepen I, Quirynen M. Probiotics and oral healthcare. Periodontology 2000. 2008;48:111–47. [DOI] [PubMed] [Google Scholar]
- [34].Zidar A, Kristl J, Kocbek P, Zupancic S. Treatment challenges and delivery systems in immunomodulation and probiotic therapies for periodontitis. Expert Opin Drug Deliv. 2021;18:1229–44. [DOI] [PubMed] [Google Scholar]