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<article article-type="systematic-review" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Oral. Health</journal-id>
<journal-title>Frontiers in Oral Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Oral. Health</abbrev-journal-title>
<issn pub-type="epub">2673-4842</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/froh.2025.1535233</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Oral Health</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Unveiling the dual nature of <italic>Lactobacillus</italic>: from cariogenic threat to probiotic protector&#x2014;a critical review with bibliometric analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Fu</surname><given-names>Di</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="an1"><sup>&#x2020;</sup></xref><role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/><role content-type="https://credit.niso.org/contributor-roles/data-curation/"/><role content-type="https://credit.niso.org/contributor-roles/visualization/"/><role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Shu</surname><given-names>Xingyue</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="an1"><sup>&#x2020;</sup></xref><role content-type="https://credit.niso.org/contributor-roles/data-curation/"/><role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/><role content-type="https://credit.niso.org/contributor-roles/project-administration/"/><role content-type="https://credit.niso.org/contributor-roles/validation/"/><role content-type="https://credit.niso.org/contributor-roles/visualization/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Yao</surname><given-names>Lin</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role content-type="https://credit.niso.org/contributor-roles/data-curation/"/><role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/><role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/></contrib>
<contrib contrib-type="author"><name><surname>Zhou</surname><given-names>Ge</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Ji</surname><given-names>Mengzhen</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author"><name><surname>Liao</surname><given-names>Ga</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1836563/overview"/><role content-type="https://credit.niso.org/contributor-roles/methodology/"/><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Zhu</surname><given-names>Yunwo</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Zou</surname><given-names>Ling</given-names></name>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><uri xlink:href="https://loop.frontiersin.org/people/2815373/overview" /><role content-type="https://credit.niso.org/contributor-roles/supervision/"/><role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/></contrib>
</contrib-group>
<aff id="aff1"><label><sup>1</sup></label><institution>State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University</institution>, <addr-line>Chengdu, Sichuan</addr-line>, <country>China</country></aff>
<aff id="aff2"><label><sup>2</sup></label><institution>Department of Information Management, Department of Stomatology Informatics, West China Hospital of Stomatology, Sichuan University</institution>, <addr-line>Chengdu</addr-line>, <country>China</country></aff>
<aff id="aff3"><label><sup>3</sup></label><institution>State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University</institution>, <addr-line>Chengdu, Sichuan</addr-line>, <country>China</country></aff>
<aff id="aff4"><label><sup>4</sup></label><institution>State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Conservative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University</institution>, <addr-line>Chengdu, Sichuan</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p><bold>Edited by:</bold> Keke Zhang, Wenzhou Medical University, China</p></fn>
<fn fn-type="edited-by"><p><bold>Reviewed by:</bold> Yuan Liu, Temple University, United States</p>
<p>Wen Zhou, Fujian Medical University, China</p></fn>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Yunwo Zhu <email>zhuyunwo@163.com</email> Ling Zou <email>zouling@scu.edu.cn</email></corresp>
<fn fn-type="equal" id="an1"><label><sup>&#x2020;</sup></label><p>These authors have contributed equally to this work</p></fn>
</author-notes>
<pub-date pub-type="epub"><day>31</day><month>01</month><year>2025</year></pub-date>
<pub-date pub-type="collection"><year>2025</year></pub-date>
<volume>6</volume><elocation-id>1535233</elocation-id>
<history>
<date date-type="received"><day>27</day><month>11</month><year>2024</year></date>
<date date-type="accepted"><day>13</day><month>01</month><year>2025</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2025 Fu, Shu, Yao, Zhou, Ji, Liao, Zhu and Zou.</copyright-statement>
<copyright-year>2025</copyright-year><copyright-holder>Fu, Shu, Yao, Zhou, Ji, Liao, Zhu and Zou</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<abstract><sec><title>Introduction</title>
<p>Dental caries is a prevalent oral disease with a multifactorial etiology. <italic>Lactobacillus</italic> has been implicated in caries progression on account of its acidogenic properties; On the other hand, they constitute one of the potential probiotic strategies for preventing dental caries. This complex relationship renders the relationship between <italic>Lactobacillus</italic> and dental caries remains ambiguous.</p>
</sec><sec><title>Methods</title>
<p>The Web of Science core collections (WoSCC) were searched to acquire articles relevant to <italic>Lactobacillus</italic> and dental caries. After retrieval and manual screening, publications were analyzed by VOSviewer.</p>
</sec><sec><title>Results</title>
<p>Sweden, the US, and China, which have been the center of international cooperation, have produced the most publications in the research area. Caries Research is the main counterpart journal in the field. &#x201C;Dental caries&#x201D;, &#x201C;<italic>Streptococcus mutans</italic>&#x201D;, &#x201C;Lactobacilli&#x201D;, &#x201C;Probiotics&#x201D;, and &#x201C;Children&#x201D; have been commonly used as keywords.</p>
</sec><sec><title>Discussion</title>
<p>Based on bibliometric analysis, this study reviews the relationship between lactobacilli and dental caries, emphasizing their dual roles. The detection rate of lactobacilli is closely associated with the incidence and severity of dental caries. However, under specific environmental conditions, these bacteria also exhibit potential probiotic properties that may aid in the prevention of dental caries. Additionally, <italic>Lactobacillu</italic>s is strongly associated with early childhood caries, a specific type of caries.</p>
</sec>
</abstract>
<kwd-group>
<kwd>lactobacilli</kwd>
<kwd>dental caries</kwd>
<kwd>cariogenicity</kwd>
<kwd>probiotics</kwd>
<kwd>caries prevention</kwd>
<kwd>early childhood caries</kwd>
<kwd>bibliometrics</kwd>
</kwd-group><contract-num rid="cn001">82071111</contract-num><contract-sponsor id="cn001">National Natural Science Foundation of China</contract-sponsor><counts>
<fig-count count="4"/>
<table-count count="8"/><equation-count count="0"/><ref-count count="93"/><page-count count="12"/><word-count count="0"/></counts><custom-meta-wrap><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Preventive Dentistry</meta-value></custom-meta></custom-meta-wrap>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><label>1</label><title>Introduction</title>
<p>As a prevalent oral disease with a multifactorial etiology, dental caries have become a significant burden on the public health prevention system (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>). According to the World Health Organization, it is estimated that approximately 2.3 billion people worldwide are afflicted with dental caries of permanent teeth and 530 million children have caries of primary teeth (<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>). Dental plaque refers to the bacterial biofilm attached to the surface of teeth, which is one of the causes of caries and one of the main goals of caries prevention and treatment.</p>
<p>It is postulated that the bacteria of the genus <italic>Lactobacillus</italic> play a crucial role in the further development of caries, particularly in dentin (<xref ref-type="bibr" rid="B5">5</xref>). They have consistently been identified at caries sites, whether in the past through traditional clinical isolation and cultivation technology (<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B7">7</xref>), later with 16S sequence analysis (<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B9">9</xref>), or more recently with deep sequencing (<xref ref-type="bibr" rid="B10">10</xref>). In recent years, research on <italic>Lactobacillus</italic> has shifted from its cariogenicity to the potential of anti-cariogenic probiotics. They constitute one of the potential probiotic approaches for the prevention of dental caries, which has been demonstrated both <italic>in vitro</italic> (<xref ref-type="bibr" rid="B11">11</xref>) and in clinical studies (<xref ref-type="bibr" rid="B12">12</xref>).</p>
<p>This complex relationship renders the study of <italic>Lactobacillus</italic> and dental caries less clear than that of <italic>Streptococcus mutans</italic>. The pathogenic mechanisms and specific contributions of lactobacilli are still subjects of debate. Against this backdrop, conducting a review of existing literature to elucidate the current state of research, and identifying hot topics is essential. This review aims to comprehensively analyze the research landscape of <italic>Lactobacillus</italic> in the context of dental caries, emphasizing its pathogenesis, epidemiology, and potential therapeutic applications. By critically evaluating existing findings, the review seeks to identify knowledge gaps, inspire innovative experimental approaches, and optimize research resource allocation.</p>
<p>Bibliometrics, a crucial research methodology, provides a comprehensive and systematic perspective through the analysis of the quantity and trends within a considerable body of relevant literature (<xref ref-type="bibr" rid="B13">13</xref>). Via statistical and quantitative analysis, bibliometrics facilitates the identification of trending topics, clarification of the trajectory of disciplinary development, and provision of crucial reference points for the academic community and decision-makers (<xref ref-type="bibr" rid="B14">14</xref>). In the field of dentistry, bibliometrics has been applied to research areas such as root caries (<xref ref-type="bibr" rid="B15">15</xref>), orthodontics (<xref ref-type="bibr" rid="B16">16</xref>), and oral oncology (<xref ref-type="bibr" rid="B17">17</xref>). To the best of our knowledge, there is currently no bibliometric analysis conducted in the research field related to lactobacilli and dental caries.</p>
</sec>
<sec id="s2" sec-type="methods"><label>2</label><title>Materials and methods</title>
<sec id="s2a"><label>2.1</label><title>Search strategy</title>
<p>The search was performed on March 18, 2024, on the Web of Science Core Collections (WoSCC) database. When performing a bibliometric analysis, WoSCC is one of the most popular scientific source databases for the superiority of supplying data for reference analysis. The retrieval was Topic&#x2009;&#x003D;&#x2009;(dental caries) AND Title&#x2009;&#x003D;&#x2009;(Lactobacilli OR Lactobacillus). The inclusion criteria for this analysis were original research articles that explored the role of <italic>Lactobacillus</italic> in dental caries, either in terms of prevention or progression. Exclusion criteria included studies that did not involve <italic>Lactobacillus</italic> or dental caries, those that did not report caries-related outcomes, and studies that were non-peer-reviewed or just abstracts or reviews. The full record and cited references of the retrieved articles were exported in plain text format for subsequent analyses.</p>
</sec>
<sec id="s2b"><label>2.2</label><title>Data selection strategy</title>
<p>The article selection process followed a previously reported methodology (<xref ref-type="bibr" rid="B18">18</xref>). In brief, two independent reviewers (D.F and L.Y) conducted an autonomous screening of titles and abstracts, and when required, evaluated full texts to identify pertinent studies. Disagreements between the two reviewers were resolved through discussions facilitated by a third reviewer with substantial experience (L.Z).</p>
</sec>
<sec id="s2c"><label>2.3</label><title>Data analysis tool</title>
<p>The final included literature was exported and analyzed using the professional bibliometric analysis software VOSviewer, owing to its capability to generate clear and easily interpretable visualizations (<xref ref-type="bibr" rid="B19">19</xref>).</p>
</sec>
</sec>
<sec id="s3" sec-type="results"><label>3</label><title>Results</title>
<sec id="s3a"><label>3.1</label><title>Number of publications</title>
<p>A total of 274 articles related to <italic>Lactobacillus</italic> and dental caries were retrieved. After screening, 21 articles were excluded (unrelated to dental caries&#x2009;&#x003D;&#x2009;16, non-article&#x2009;&#x003D;&#x2009;5). A total of 253 articles on <italic>Lactobacillus</italic> and dental caries were published and indexed in WoSCC, and the number of publications was generally on the increase (<xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>).</p>
<fig id="F1" position="float"><label>Figure 1</label>
<caption><p>Number of publications relevant to <italic>Lactobacillus</italic> and dental caries.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1535233-g001.tif"/>
</fig>
</sec>
<sec id="s3b"><label>3.2</label><title>The analysis of countries</title>
<p><xref ref-type="table" rid="T1">Table&#x00A0;1</xref> shows the top 10 most productive countries in the <italic>Lactobacillus</italic> and dental caries research area. Sweden emerged as the country with the highest publications (<italic>n</italic>&#x2009;&#x003D;&#x2009;34), followed by China (24) and the USA (22). <xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref> illustrates the collaboration among 17 countries with more than 4 publications. Each node in the graph represents a country. Nodes of the same color indicate countries belonging to the same cluster. The lines between nodes represent collaborative relationships between the corresponding countries.</p>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>The top 10 productive countries and institutions.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="left"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Countries</th>
<th valign="top" align="center">Record count</th>
<th valign="top" align="center">Affiliation</th>
<th valign="top" align="center">Record count</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Sweden</td>
<td valign="top" align="center">34</td>
<td valign="top" align="left">University of Gothenburg</td>
<td valign="top" align="center">16</td>
</tr>
<tr>
<td valign="top" align="left">China</td>
<td valign="top" align="center">24</td>
<td valign="top" align="left">Prince of Songkla University</td>
<td valign="top" align="center">15</td>
</tr>
<tr>
<td valign="top" align="left">USA</td>
<td valign="top" align="center">22</td>
<td valign="top" align="left">University of Turku</td>
<td valign="top" align="center">11</td>
</tr>
<tr>
<td valign="top" align="left">Thailand</td>
<td valign="top" align="center">16</td>
<td valign="top" align="left">Umea University</td>
<td valign="top" align="center">9</td>
</tr>
<tr>
<td valign="top" align="left">India</td>
<td valign="top" align="center">15</td>
<td valign="top" align="left">University of Copenhagen</td>
<td valign="top" align="center">8</td>
</tr>
<tr>
<td valign="top" align="left">Brazil</td>
<td valign="top" align="center">13</td>
<td valign="top" align="left">University of London</td>
<td valign="top" align="center">8</td>
</tr>
<tr>
<td valign="top" align="left">Finland</td>
<td valign="top" align="center">13</td>
<td valign="top" align="left">University of Amsterdam</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">Iran</td>
<td valign="top" align="center">12</td>
<td valign="top" align="left">Tanbah University</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">South Korea</td>
<td valign="top" align="center">12</td>
<td valign="top" align="left">University of Sydney</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">UK</td>
<td valign="top" align="center">11</td>
<td valign="top" align="left">Egyptian Knowledge Bank</td>
<td valign="top" align="center">4</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F2" position="float"><label>Figure 2</label>
<caption><p>The cooperative network of countries in the <italic>Lactobacillus</italic> and dental caries research area.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1535233-g002.tif"/>
</fig>
<p>Sweden, as the leading contributor in terms of publications, focuses its research primarily on two key areas: (1) the potential anti-caries properties of <italic>Lactobacillus</italic> as probiotics, including their effects on cariogenic pathogens such as <italic>S. mutans</italic> (<xref ref-type="bibr" rid="B20">20</xref>, <xref ref-type="bibr" rid="B21">21</xref>) and their preventive efficacy in various populations, such as orthodontic patients, children with early caries lesions, high-caries-risk schoolchildren, and elderly individuals with root caries (<xref ref-type="bibr" rid="B22">22</xref>&#x2013;<xref ref-type="bibr" rid="B25">25</xref>); (2) the load, and genotypes of <italic>Lactobacillus</italic> species in the oral environment or carious sites (<xref ref-type="bibr" rid="B26">26</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>). The United States, the second-largest contributor to the publications, has placed particular emphasis on the interactions between various <italic>Lactobacillus</italic> species and other oral microorganisms, such as <italic>S. mutans</italic>, <italic>Candida albicans</italic> biofilms, and even multispecies biofilms (<xref ref-type="bibr" rid="B30">30</xref>&#x2013;<xref ref-type="bibr" rid="B35">35</xref>).</p>
</sec>
<sec id="s3c"><label>3.3</label><title>The analysis of institutions</title>
<p><xref ref-type="table" rid="T1">Table&#x00A0;1</xref> includes the top 10 institutions with the largest number of publications, with the University of Gothenburg being the only institution having more than 15 publications followed by Prince of Songkla University (15) and University of Turku (11).</p>
</sec>
<sec id="s3d"><label>3.4</label><title>The analysis of authors</title>
<p>The top 10 most productive authors are shown in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>. Teanpaisan R (15) emerge as the author with the highest publications, followed by Piwat S (11) and Twetman S (10). Besides, Twetman S acquires the highest 51&#x2005;h-index. Teanpaisan R and Piwat S are affiliated with the same research institution, Prince Songkla University. Their research primarily focuses on the probiotic potential of <italic>Lactobacillus</italic>, particularly strains like <italic>L. rhamnosus SD11</italic> and <italic>L. paracasei SD1</italic> (<xref ref-type="bibr" rid="B36">36</xref>&#x2013;<xref ref-type="bibr" rid="B41">41</xref>). Twetman&#x0027;s work has involved the use of <italic>L. reuteri</italic> and <italic>L. rhamnosus</italic> in the prevention of caries (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B42">42</xref>, <xref ref-type="bibr" rid="B43">43</xref>). In addition, his research has explored the potential of probiotics to bind fluoride (<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B44">44</xref>).</p>
<table-wrap id="T2" position="float"><label>Table 2</label>
<caption><p>The top 10 productive authors.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Author</th>
<th valign="top" align="center">Affiliation</th>
<th valign="top" align="center">H-index</th>
<th valign="top" align="center">Record count</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Teanpaisan, Rawee</td>
<td valign="top" align="left">Prince of Songkla University</td>
<td valign="top" align="center">26</td>
<td valign="top" align="center">15</td>
</tr>
<tr>
<td valign="top" align="left">Piwat, Supatcharin</td>
<td valign="top" align="left">Prince of Songkla University</td>
<td valign="top" align="center">17</td>
<td valign="top" align="center">11</td>
</tr>
<tr>
<td valign="top" align="left">Twetman, Svante</td>
<td valign="top" align="left">University of Copenhagen</td>
<td valign="top" align="center">51</td>
<td valign="top" align="center">10</td>
</tr>
<tr>
<td valign="top" align="left">Soderling, Eva</td>
<td valign="top" align="left">University of Turku</td>
<td valign="top" align="center">30</td>
<td valign="top" align="center">7</td>
</tr>
<tr>
<td valign="top" align="left">Tenovuo, Jorma</td>
<td valign="top" align="left">University of Turku</td>
<td valign="top" align="center">44</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">Pahumunto, Nuntiya</td>
<td valign="top" align="left">Prince of Songkla University</td>
<td valign="top" align="center">10</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Kohler, Brady</td>
<td valign="top" align="left">University of Nebraska Lincoln</td>
<td valign="top" align="center">33</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Xiao, Jin</td>
<td valign="top" align="left">University of Rochester</td>
<td valign="top" align="center">12</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Stecksen-Blicks, Christina</td>
<td valign="top" align="left">Umea University</td>
<td valign="top" align="center">22</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Beighton, David</td>
<td valign="top" align="left">King&#x0027;s College London</td>
<td valign="top" align="center">52</td>
<td valign="top" align="center">4</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3e"><label>3.5</label><title>The analysis of journals</title>
<p>A total of 133 journals in the WoSCC database published studies relevant to <italic>Lactobacillus</italic> and dental caries. <xref ref-type="table" rid="T3">Table&#x00A0;3</xref> shows the top 10 journals by the number of publications. Caries Research is the number one source with 24 articles, followed by Archives of Oral Biology with 20 articles and Journal of Dental Research with 10 articles.</p>
<table-wrap id="T3" position="float"><label>Table 3</label>
<caption><p>The top 10 productive journals.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Journal</th>
<th valign="top" align="center">IF</th>
<th valign="top" align="center">Record count</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Caries Research</td>
<td valign="top" align="center">4.2</td>
<td valign="top" align="center">24</td>
</tr>
<tr>
<td valign="top" align="left">Archives of Oral Biology</td>
<td valign="top" align="center">3</td>
<td valign="top" align="center">20</td>
</tr>
<tr>
<td valign="top" align="left">Journal of Dental Research</td>
<td valign="top" align="center">7.6</td>
<td valign="top" align="center">10</td>
</tr>
<tr>
<td valign="top" align="left">Acta Odontologica Scandinavica</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">8</td>
</tr>
<tr>
<td valign="top" align="left">Oral Microbiology and Immunology</td>
<td valign="top" align="center">2.807</td>
<td valign="top" align="center">8</td>
</tr>
<tr>
<td valign="top" align="left">Clinical Oral Investigations</td>
<td valign="top" align="center">3.4</td>
<td valign="top" align="center">6</td>
</tr>
<tr>
<td valign="top" align="left">Community Dentistry and Oral Epidemiology</td>
<td valign="top" align="center">2.3</td>
<td valign="top" align="center">6</td>
</tr>
<tr>
<td valign="top" align="left">Journal of Dental Sciences</td>
<td valign="top" align="center">3.5</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">Microbial Pathogenesis</td>
<td valign="top" align="center">3.8</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Anaerobe</td>
<td valign="top" align="center">2.3</td>
<td valign="top" align="center">3</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3f"><label>3.6</label><title>The analysis of keywords</title>
<p>The top 20 occurrent keywords are listed in <xref ref-type="table" rid="T4">Table&#x00A0;4</xref>. The &#x201C;dental caries&#x201D;, &#x201C;<italic>Streptococcus mutans</italic>&#x201D;, &#x201C;lactobacilli&#x201D;, &#x201C;probiotics&#x201D;, and &#x201C;children&#x201D; are the most used keywords. In VOSviewer, setting the minimum of occurrences of a keyword as 8, 45 keywords that met the requirement were used to depict the co-occurrence map (<xref ref-type="fig" rid="F3">Figure&#x00A0;3</xref>). Nodes of the color correspond to the average time of the keywords appear. The lines between nodes represent the occurrence relationship. <xref ref-type="table" rid="T4">Table&#x00A0;4</xref>; <xref ref-type="fig" rid="F3">Figure&#x00A0;3</xref> shows the hot topics in the field of <italic>Lactobacillus</italic> and dental caries. The keywords &#x201C;colonization,&#x201D; &#x201C;adherence,&#x201D; &#x201C;virulence,&#x201D; and &#x201C;pH&#x201D; highlight a significant research focus on the pathogenic mechanisms of <italic>Lactobacillus</italic> in dental caries, while terms like &#x201C;prevalence,&#x201D; &#x201C;strains,&#x201D; and &#x201C;risk&#x201D; underscore efforts to elucidate the relationship between the abundance and distribution of <italic>Lactobacillus</italic> and the epidemiological characteristics of dental caries; (2) The frequent mention of the keyword &#x201C;probiotics&#x201D;, &#x201C;prevention&#x201D; and &#x201C;milk&#x201D; suggests a growing interest in exploring the potential probiotic effects of <italic>Lactobacillus</italic> in caries prevention and management; (3) early childhood caries (ECC).</p>
<table-wrap id="T4" position="float"><label>Table 4</label>
<caption><p>The top 20 occurrent keywords.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="left"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Keyword</th>
<th valign="top" align="center">Occurrence</th>
<th valign="top" align="center">Keyword</th>
<th valign="top" align="center">Occurrence</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Dental caries</td>
<td valign="top" align="center">174</td>
<td valign="top" align="left">lactobacillus rhamnosus</td>
<td valign="top" align="center">25</td>
</tr>
<tr>
<td valign="top" align="left">Streptococcus mutans</td>
<td valign="top" align="center">139</td>
<td valign="top" align="left">prevalence</td>
<td valign="top" align="center">24</td>
</tr>
<tr>
<td valign="top" align="left">Lactobacilli</td>
<td valign="top" align="center">87</td>
<td valign="top" align="left">strains</td>
<td valign="top" align="center">24</td>
</tr>
<tr>
<td valign="top" align="left">Probiotics</td>
<td valign="top" align="center">69</td>
<td valign="top" align="left">health</td>
<td valign="top" align="center">23</td>
</tr>
<tr>
<td valign="top" align="left">Children</td>
<td valign="top" align="center">51</td>
<td valign="top" align="left"><italic>in vitro</italic></td>
<td valign="top" align="center">23</td>
</tr>
<tr>
<td valign="top" align="left">Dental plaque</td>
<td valign="top" align="center">44</td>
<td valign="top" align="left">growth</td>
<td valign="top" align="center">21</td>
</tr>
<tr>
<td valign="top" align="left">Bacteria</td>
<td valign="top" align="center">41</td>
<td valign="top" align="left">lactobacillus reuteri</td>
<td valign="top" align="center">20</td>
</tr>
<tr>
<td valign="top" align="left">Saliva</td>
<td valign="top" align="center">40</td>
<td valign="top" align="left">adherence</td>
<td valign="top" align="center">17</td>
</tr>
<tr>
<td valign="top" align="left">Biofilms</td>
<td valign="top" align="center">36</td>
<td valign="top" align="left">colonization</td>
<td valign="top" align="center">16</td>
</tr>
<tr>
<td valign="top" align="left">Milk</td>
<td valign="top" align="center">35</td>
<td valign="top" align="left">prevention</td>
<td valign="top" align="center">16</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F3" position="float"><label>Figure 3</label>
<caption><p>The co-occurrence analysis of keywords in the <italic>Lactobacillus</italic> and dental caries research area.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1535233-g003.tif"/>
</fig>
</sec>
<sec id="s3g"><label>3.7</label><title>The analysis of highly cited articles</title>
<p>Information on the top ten highly cited articles is presented in <xref ref-type="table" rid="T5">Table&#x00A0;5</xref>. The most frequently cited article, with 376 citations, was a long-term clinical follow-up study of <italic>L. rhamnoses</italic> used in children with caries or high caries risk (<xref ref-type="bibr" rid="B45">45</xref>). The second most cited article, with 269 citations, was a study published in 2004 by Byun et al., which explored the genetic diversity of lactobacilli at advanced dental caries based on 16S ribosomal DNA technology (<xref ref-type="bibr" rid="B8">8</xref>).</p>
<table-wrap id="T5" position="float"><label>Table 5</label>
<caption><p>The details of the top 10 highest-cited articles.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">First author</th>
<th valign="top" align="center">Title</th>
<th valign="top" align="center">Year</th>
<th valign="top" align="center">Cited time</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">N&#x00E4;se, L</td>
<td valign="top" align="left">Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children.</td>
<td valign="top" align="center">2001</td>
<td valign="top" align="center">376</td>
</tr>
<tr>
<td valign="top" align="left">Byun, R</td>
<td valign="top" align="left">Quantitative analysis of diverse Lactobacillus species present in advanced dental caries.</td>
<td valign="top" align="center">2004</td>
<td valign="top" align="center">269</td>
</tr>
<tr>
<td valign="top" align="left">IKEDA, T</td>
<td valign="top" align="left">Changes in streptococcus-mutans and lactobacilli in plaque in relation to initiation of dental-caries in negro children.</td>
<td valign="top" align="center">1973</td>
<td valign="top" align="center">178</td>
</tr>
<tr>
<td valign="top" align="left">Nikawa, H</td>
<td valign="top" align="left">Lactobacillus reuteri in bovine milk fermented decreases the oral carriage of mutans streptococci.</td>
<td valign="top" align="center">2004</td>
<td valign="top" align="center">146</td>
</tr>
<tr>
<td valign="top" align="left">Wasfi, R</td>
<td valign="top" align="left">Probiotic Lactobacillus sp inhibit growth, biofilm formation and gene expression of caries-inducing Streptococcus mutans.</td>
<td valign="top" align="center">2018</td>
<td valign="top" align="center">143</td>
</tr>
<tr>
<td valign="top" align="left">Kr&#x00FC;ger, C</td>
<td valign="top" align="left">In situ delivery of passive immunity by lactobacilli producing single-chain antibodies.</td>
<td valign="top" align="center">2002</td>
<td valign="top" align="center">143</td>
</tr>
<tr>
<td valign="top" align="left">KOHLER, B</td>
<td valign="top" align="left">The effect of caries-preventive measures in mothers on dental-caries and the oral presence of the bacteria streptococcus-mutans and lactobacilli in their children.</td>
<td valign="top" align="center">1984</td>
<td valign="top" align="center">130</td>
</tr>
<tr>
<td valign="top" align="left">Stecks&#x00E9;n-Blicks, C</td>
<td valign="top" align="left">Effect of Long-Term Consumption of Milk Supplemented with Probiotic Lactobacilli and Fluoride on Dental Caries and General Health in Preschool Children: A Cluster-Randomized Study.</td>
<td valign="top" align="center">2009</td>
<td valign="top" align="center">125</td>
</tr>
<tr>
<td valign="top" align="left">&#x00C7;aglar, E</td>
<td valign="top" align="left">Effect of chewing gums containing xylitol or probiotic bacteria on salivary mutans streptococci and lactobacilli.</td>
<td valign="top" align="center">2007</td>
<td valign="top" align="center">97</td>
</tr>
<tr>
<td valign="top" align="left">Simark-Mattsson, C</td>
<td valign="top" align="left">Lactobacillus-mediated interference of mutans streptococci in caries-free vs. caries-active subjects.</td>
<td valign="top" align="center">2007</td>
<td valign="top" align="center">90</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><label>4</label><title>Discussion</title>
<p>To the best of our knowledge, this is the inaugural study to apply bibliometric analysis to the research domains of <italic>Lactobacillus</italic> and dental caries. Our review analyzes the relationship between lactobacilli and dental caries through the lens of visualized bibliometrics, evaluating the current state and future directions of this field based on empirical evidence rather than subjective opinions.</p>
<p>The increasing number of publications on the relationship between dental caries and lactobacilli over the years indicates a growing interest in this topic, suggesting that it is emerging as a significant research focus. The rising importance of dental caries prevention in clinical practice and public health may stimulate the research area. Cooperation between countries in <italic>Lactobacillus</italic> and dental caries research area predominantly concentrated among a few scientifically advanced nations, such as the United States, Sweden, which occupy central positions in the collaboration network. Authors such as Teanpaisan R, Piwat S, and Twetman S, with a high yield, may be leading figures in the research field of lactobacilli and dental caries, playing a significant role in driving progress and fostering innovation in this domain.</p>
<p>As mentioned in the results, the hot topics in the field of <italic>Lactobacillus</italic> and dental caries include the following three (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>).</p>
<fig id="F4" position="float"><label>Figure 4</label>
<caption><p>Major research hotspots in the field of <italic>Lactobacillus</italic> and dental caries. The cariogenic potential of <italic>Lactobacillus</italic> is primarily attributed to its acidogenicity, aciduricity, collagen adhesion properties, and biofilm-forming capacity. However, certain <italic>Lactobacillus</italic> strains may exhibit protective effects against dental caries by producing bacteriocins, H&#x2082;O&#x2082;, and organic acids, facilitating competitive adhesion and colonization, inhibiting cariogenic biofilms, and modulating the host immune response. Created with <ext-link ext-link-type="uri" xlink:href="https://Biorender.com">Biorender.com</ext-link>.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="froh-06-1535233-g004.tif"/>
</fig>
<sec id="s4a"><label>4.1</label><title>Pathogenesis and epidemiology of <italic>Lactobacillus</italic> in dental caries</title>
<p>The cariogenic virulence of <italic>Lactobacillus</italic> has been summarized in the literature (<xref ref-type="bibr" rid="B46">46</xref>&#x2013;<xref ref-type="bibr" rid="B48">48</xref>). The cariogenic potential of <italic>Lactobacillus</italic> is primarily attributed to its acidogenicity, aciduricity, adhesion collagen properties, and biofilm-forming capacity (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>). Lactobacilli possess a diverse array of enzymes, including glycoside hydrolases, glycosyltransferases, and isomerases, which enable them to metabolize a wide range of carbohydrates, particularly the oligosaccharides and starches abundant in the oral cavity, resulting in acid production (<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B49">49</xref>). Various <italic>Lactobacillus</italic> species, including <italic>L. plantarum</italic>, <italic>L.salivarius</italic>, <italic>L. rhamnosus</italic>, and <italic>L. casei/paracasei</italic>, have demonstrated the ability to reduce the pH to the critical threshold for enamel demineralization (pH 5.5) within 2.5&#x2013;3&#x2005;h (<xref ref-type="bibr" rid="B50">50</xref>). <italic>Lactobacillus</italic> species have evolved complex physiological and molecular mechanisms to survive and adapt to acid stress. These mechanisms include modifications to the cell membrane, activation of ATPase proton pumps, metabolic regulation, and the production of macromolecular protective and repair proteins (<xref ref-type="bibr" rid="B51">51</xref>). <italic>Lactobacillus</italic> species exhibit relatively limited biofilm formation capabilities and weak adhesion to healthy tooth surfaces (<xref ref-type="bibr" rid="B31">31</xref>, <xref ref-type="bibr" rid="B52">52</xref>, <xref ref-type="bibr" rid="B53">53</xref>). However, it is noteworthy that when <italic>S. mutans</italic> and/or other early colonizers establish retention sites, the biofilm formation of <italic>Lactobacillus</italic> significantly increases (<xref ref-type="bibr" rid="B31">31</xref>, <xref ref-type="bibr" rid="B54">54</xref>).</p>
<p>From an epidemiological point of view, the abundance and diversity of <italic>Lactobacillus</italic> are closely related to caries risk. Based on previous literature (<xref ref-type="bibr" rid="B46">46</xref>, <xref ref-type="bibr" rid="B54">54</xref>, <xref ref-type="bibr" rid="B55">55</xref>), we further summarized the species of <italic>Lactobacillus</italic> detected at caries sites (<xref ref-type="table" rid="T6">Table&#x00A0;6</xref>). It can be seen that the types of <italic>Lactobacillus</italic> detected in different populations/individuals are different.</p>
<table-wrap id="T6" position="float"><label>Table 6</label>
<caption><p>Species of lactobacilli identified in caries.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Identified species</th>
<th valign="top" align="center">Ozaki et al.</th>
<th valign="top" align="center">Botha et al.</th>
<th valign="top" align="center">Martin et al.</th>
<th valign="top" align="center">Buyn et al.</th>
<th valign="top" align="center">Munson et al.</th>
<th valign="top" align="center">Chhour et al.</th>
<th valign="top" align="center">Sch&#x00FC;pbach et al.</th>
<th valign="top" align="center">Hahn et al.</th>
<th valign="top" align="center">Chavez de Paz et al.</th>
<th valign="top" align="center">Obata et al.</th>
<th valign="top" align="center">Kianoush et al.</th>
<th valign="top" align="center">Nancy et al.</th>
<th valign="top" align="center">Marchant et al.</th>
<th valign="top" align="center">Becker et al.</th>
</tr>
<tr>
<th valign="top" align="center"/>
<th valign="top" align="center" colspan="11">Adult</th>
<th valign="top" align="center" colspan="3">Children</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left"><italic>L. rhamnosus</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;&#x002B;</td>
<td valign="top" align="center">24&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L.fermentum</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">19&#x0025;</td>
<td valign="top" align="center">&#x002B;</td>
</tr>
<tr>
<td valign="top" align="left"><italic>L. casei</italic></td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">38&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. gasseri</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. salivarius</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">7&#x0025;</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. paracasei</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. plantarum</italic></td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">-</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">-</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. crispatus</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. acidophilus</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. delbrueckii</italic></td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">NI</td>
<td valign="top" align="center"/>
</tr>
<tr>
<td valign="top" align="left"><italic>L. cellobiosus</italic></td>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center">&#x2212;</td>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center"/>
<td valign="top" align="center">&#x002B;</td>
<td valign="top" align="center">34&#x0025;</td>
<td valign="top" align="center"/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn1"><p>NI, non identifiable with the method used; &#x2212;, non recovered.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>Although <italic>Lactobacillus</italic> is frequently detected in the mouths of children with dental caries, it has not yet been definitively proven that the high detection rate of <italic>Lactobacillus</italic> directly leads to the development of caries. Some views suggest that <italic>Lactobacillus</italic> does not possess the conditions necessary to cause caries. On the contrary, the high detection rate may be more of a passive result of <italic>Lactobacillus</italic> being retained at the site of the lesion after caries develops (<xref ref-type="bibr" rid="B53">53</xref>, <xref ref-type="bibr" rid="B54">54</xref>, <xref ref-type="bibr" rid="B56">56</xref>). Future research should further explore the causal relationship between <italic>Lactobacillus</italic> and caries, considering its potential multiple mechanisms of action.</p>
</sec>
<sec id="s4b"><label>4.2</label><title><italic>Lactobacillus</italic> has the probiotic potential of anti-caries</title>
<p>In recent years, probiotics have gained increasing attention in the prevention and treatment of dental caries biofilms. Numerous <italic>in vitro</italic>, animal, and clinical studies have demonstrated the significant potential of <italic>Lactobacillus</italic> in anti-caries activity. We have summarized these studies in <xref ref-type="table" rid="T7">Table&#x00A0;7</xref> for the reader&#x0027;s reference. Certain <italic>Lactobacillus</italic> strains might demonstrate protective effects against caries through the production of bacteriocin (<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B70">70</xref>), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and organic acid (<xref ref-type="bibr" rid="B71">71</xref>), competitive adhesion and colonization (<xref ref-type="bibr" rid="B72">72</xref>), inhibition of cariogenic biofilms (<xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B73">73</xref>), and regulation of the host immune system (<xref ref-type="bibr" rid="B32">32</xref>, <xref ref-type="bibr" rid="B41">41</xref>, <xref ref-type="bibr" rid="B74">74</xref>) (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>).</p>
<table-wrap id="T7" position="float"><label>Table 7</label>
<caption><p>Studies related to the anti-caries effect of probiotics <italic>Lactobacillus.</italic></p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Type</th>
<th valign="top" align="center">Author, year</th>
<th valign="top" align="center">Species</th>
<th valign="top" align="center">Study object</th>
<th valign="top" align="center">Main conclusions</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="12"><italic>in vitro</italic></td>
<td valign="top" align="left">Wu et al. 2015 (<xref ref-type="bibr" rid="B11">11</xref>)</td>
<td valign="top" align="left"><italic>L. salivarius</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left"><italic>L. salivarius K35 and K43</italic> effectively suppressed biofilm formation by decreasing both the population of <italic>Sm</italic> and the synthesis of exopolysaccharides.</td>
</tr>
<tr>
<td valign="top" align="left">Wasfi et al. 2018 (<xref ref-type="bibr" rid="B32">32</xref>)</td>
<td><italic>L. casei</italic>, <italic>L. reuteri</italic>, <italic>L. plantarum, L. salivarius</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left"><italic>Lactobacillus</italic> can prevent tooth decay by restricting the growth and virulence factors of <italic>Sm</italic>.</td>
</tr>
<tr>
<td valign="top" align="left">Zeng et al. 2022 (<xref ref-type="bibr" rid="B33">33</xref>)</td>
<td><italic>L. rhamnosus</italic>, <italic>L. plantarum</italic>, <italic>L. salivarius</italic></td>
<td valign="top" align="left"><italic>Sm, Ca</italic></td>
<td valign="top" align="left"><italic>L. plantarum</italic> effectively reduced biofilm formation by interfering with the symbiotic relationship between <italic>Sm</italic> and <italic>Ca</italic>.</td>
</tr>
<tr>
<td valign="top" align="left">Banakar et al. 2023 (<xref ref-type="bibr" rid="B57">57</xref>)</td>
<td><italic>L. rhamnosus GG</italic>, <italic>L. reuteri</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left">PMs from LGG and <italic>L. reuteri</italic> suppress the biofilm formation, metabolic activity, and gtfB gene expression of <italic>Sm</italic>.</td>
</tr>
<tr>
<td valign="top" align="left">Liang et al. 2023 (<xref ref-type="bibr" rid="B58">58</xref>)</td>
<td><italic>L. plantarum</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left">The antibiofilm effect of <italic>L. plantarum</italic> CFS on <italic>Sm</italic> is the result of a combined action of multiple components, with LA playing a dominant role.</td>
</tr>
<tr>
<td valign="top" align="left">Zeng et al. 2023 (<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td><italic>L. plantarum</italic></td>
<td valign="top" align="left"><italic>Sm, Ca</italic></td>
<td valign="top" align="left"><italic>L. plantarum</italic> inhibits clinical isolates of <italic>Sm</italic> and <italic>Ca</italic>, with its antimicrobial peptide plantaricin effectively suppressing their growth.</td>
</tr>
<tr>
<td valign="top" align="left">Gu et al. 2022 (<xref ref-type="bibr" rid="B59">59</xref>)</td>
<td><italic>L. paragasseri</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left">Two purified compounds of <italic>L. paracasei</italic>, iminosugars and glycerol, can inhibit the expression of genes related to biofilm synthesis.</td>
</tr>
<tr>
<td valign="top" align="left">Luan et al. 2022 (<xref ref-type="bibr" rid="B60">60</xref>)</td>
<td><italic>L. curvatus</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left"><italic>L. curvatus</italic> and <italic>Pediococcus pentosaceus</italic> AC1-2 can form aggregates with <italic>Sm</italic>, effectively preventing its colonization.</td>
</tr>
<tr>
<td valign="top" align="left">Jung et al. 2022 (<xref ref-type="bibr" rid="B61">61</xref>)</td>
<td><italic>L. rhamnosus</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left">The combined use of prebiotic collagen peptides and the probiotic <italic>L. rhamnosus</italic> can influence the virulence of <italic>Sm</italic> in cariogenic biofilms.</td>
</tr>
<tr>
<td valign="top" align="left">Noda et al. 2021 (<xref ref-type="bibr" rid="B62">62</xref>)</td>
<td><italic>L. reuteri</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left">The presence of <italic>L. reuteri</italic> significantly reduces the glucan adhesiveness produced by <italic>Sm</italic>.</td>
</tr>
<tr>
<td valign="top" align="left">Jang et al. 2021 (<xref ref-type="bibr" rid="B63">63</xref>)</td>
<td><italic>L. brevis</italic></td>
<td valign="top" align="left"><italic>Sm</italic></td>
<td valign="top" align="left"><italic>L. brevis</italic> effectively disrupts <italic>Sm</italic> biofilm formation by inhibiting auto-aggregation, cell surface hydrophobicity, and EPS production.</td>
</tr>
<tr>
<td valign="top" align="left">Srivastava et al. 2020 (<xref ref-type="bibr" rid="B35">35</xref>)</td>
<td><italic>L. Plantarum</italic></td>
<td valign="top" align="left"><italic>Sm, Ca</italic></td>
<td valign="top" align="left"><italic>L. plantarum</italic> 108 can inhibit the biofilms of <italic>Sm</italic>, <italic>Ca</italic>, as well as their dual-species biofilm.</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="5">Animal experiments</td>
<td valign="top" align="left">Guo et al. 2023 (<xref ref-type="bibr" rid="B64">64</xref>)</td>
<td valign="top" align="left"><italic>L. paracasei ET-22</italic></td>
<td valign="top" align="left"><italic>Sm in vitro</italic>, Dental caries in mice</td>
<td valign="top" align="left">Supplementing drinking water with ET-22 significantly improves dental caries scores in mice, with both live and heat-killed ET-22 having similar effects on the microbial composition of dental plaque biofilms.</td>
</tr>
<tr>
<td valign="top" align="left">Zhang et al. 2020 (<xref ref-type="bibr" rid="B65">65</xref>)</td>
<td><italic>L. plantarum</italic></td>
<td valign="top" align="left"><italic>Sm</italic> and <italic>Ca</italic> in rats, Dental caries in mice</td>
<td valign="top" align="left"><italic>L. plantarum</italic> significantly reduces the number of <italic>Sm</italic> and <italic>Ca</italic> in the oral cavity of rats and significantly decreases enamel mineral loss.</td>
</tr>
<tr>
<td valign="top" align="left">Weng et al. 2022 (<xref ref-type="bibr" rid="B66">66</xref>)</td>
<td><italic>L. acidophilus</italic></td>
<td valign="top" align="left"><italic>Sm in vitro</italic>, Dental caries <italic>in vivo</italic> rat model</td>
<td valign="top" align="left">The outer membrane of encapsulated <italic>Lactobacillus</italic> enhances the adhesion of triclosan nanoparticles to <italic>Sm</italic> biofilms, leading to more effective targeted disruption of biofilm formation and the expression of associated virulence factors.</td>
</tr>
<tr>
<td valign="top" align="left">Zhang et al. 2020 (<xref ref-type="bibr" rid="B67">67</xref>)</td>
<td><italic>L. plantarum K41</italic></td>
<td valign="top" align="left"><italic>S. mutans in vitro and in vivo</italic> Dental caries <italic>in vivo</italic> rat model</td>
<td valign="top" align="left"><italic>L. plantarum K41</italic> effectively inhibits <italic>Sm</italic> growth, biofilm formation, and dental caries <italic>in vivo</italic>.</td>
</tr>
<tr>
<td valign="top" align="left">Lin and Pan 2014 (<xref ref-type="bibr" rid="B68">68</xref>)</td>
<td><italic>L. paracasei subsp. paracasei NTU 101</italic></td>
<td valign="top" align="left"><italic>Sm in vitro, D</italic>ental caries <italic>in vivo</italic> rat model</td>
<td valign="top" align="left">Continuous administration of NTU 101 lowered the pH of dental biofilms and reduced enamel demineralization.</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="5">Experiments on Humans</td>
<td valign="top" align="left">N&#x00E4;se et al. 2001 (<xref ref-type="bibr" rid="B45">45</xref>)</td>
<td valign="top" align="left"><italic>L. rhamnosus GG</italic></td>
<td valign="top" align="left">Children between 1 and 6 years old</td>
<td valign="top" align="left">Children who received LGG milk had less dental caries and lower <italic>Sm</italic> counts than regular milk.</td>
</tr>
<tr>
<td valign="top" align="left">Marttinen et al. 2012 (<xref ref-type="bibr" rid="B43">43</xref>)</td>
<td><italic>L. rhamnosus GG, L. reuteri</italic></td>
<td valign="top" align="left">Students of the University of Turku</td>
<td valign="top" align="left"><italic>Lactobacillus</italic> intake reduced <italic>Sm</italic> counts without significantly affecting the acidity of supragingival plaque.</td>
</tr>
<tr>
<td valign="top" align="left">Staszczyk et al. 2022 (<xref ref-type="bibr" rid="B69">69</xref>)</td>
<td><italic>L. salivarius</italic></td>
<td valign="top" align="left">Children between 3 and 6 years old</td>
<td valign="top" align="left">Two weeks of daily intake of chewable tablets containing heat-inactivated <italic>L. salivarius</italic> can significantly reduce the incidence and prevalence of dental caries in children within one year.</td>
</tr>
<tr>
<td valign="top" align="left">Pahumunto et al. 2020 (<xref ref-type="bibr" rid="B40">40</xref>)</td>
<td><italic>L. rhamnosus-SD11</italic></td>
<td valign="top" align="left">Children aged 13&#x2013;14 years old</td>
<td valign="top" align="left">Daily consumption of maltitol-containing <italic>L. reuteri</italic> SD11 fermented milk can reduce <italic>Sm</italic> in saliva, offering beneficial effects on oral health.</td>
</tr>
<tr>
<td valign="top" align="left">Pahumunto et al. 2019 (<xref ref-type="bibr" rid="B41">41</xref>)</td>
<td><italic>L. paracasei SD1</italic></td>
<td valign="top" align="left">Volunteers aged 12&#x2013;14 years old</td>
<td valign="top" align="left"><italic>L. paracasei</italic> SD1 has the ability to control <italic>Sm</italic> levels and stimulate the production of sIgA.</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn2"><p><italic>Sm</italic>, <italic>S. mutans</italic>; <italic>Ca</italic>, <italic>C. albicans</italic>; LGG, <italic>L. rhamnosus GG</italic>; PMs, postbiotic mediators; CFS, cell-free supernatant; LA, lactic acid; EPS, exopolysaccharide.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>It is important to note that while lactobacilli have been extensively studied and applied in the prevention of dental caries, the individual variability in its probiotic efficacy remains incompletely understood. Individual differences in oral microbiota, dietary habits, and genetic factors significantly influence the efficacy of lactobacilli (<xref ref-type="bibr" rid="B75">75</xref>), with notable variability observed across different age groups, regions, and health conditions, posing challenges for its clinical application. Moreover, the long-term safety of lactobacilli remains an unresolved concern. The acidogenic properties of <italic>Lactobacillus</italic> may exacerbate the acidic environment in the oral cavity under certain conditions, thereby promoting the occurrence and progression of dental caries (<xref ref-type="bibr" rid="B76">76</xref>). Additionally, the adhesive properties and biofilm-forming ability of <italic>Lactobacillus</italic> may, in some cases, synergize with other cariogenic bacteria, increasing the risk of oral microbial dysbiosis (<xref ref-type="bibr" rid="B31">31</xref>, <xref ref-type="bibr" rid="B77">77</xref>). Therefore, although <italic>Lactobacillus</italic> exhibits probiotic effects in promoting oral health, its safety in clinical applications requires further evaluation, particularly in high-risk populations such as individuals with a history of dental caries or those with compromised immune function (<xref ref-type="bibr" rid="B78">78</xref>).</p>
</sec>
<sec id="s4c"><label>4.3</label><title><italic>Lactobacillus</italic> and ECC</title>
<p>It is notable that a particular type of caries emerged in the keyword analysis: early childhood caries (ECC). ECC, defined as the existence of one or more decayed teeth that have been extracted or filled in children under the age of 6, is one of the most prevalent diseases worldwide among children of this age group (<xref ref-type="bibr" rid="B79">79</xref>). Research on the relationship between ECC and <italic>Lactobacillus</italic> can be divided into two main categories: one group explores the anti-caries effects of <italic>Lactobacillus</italic> on children with ECC, while the other investigates the load of <italic>Lactobacillus</italic> in the oral environment of children with ECC, such as in saliva and dental plaque (<xref ref-type="table" rid="T8">Table&#x00A0;8</xref>). ECC progresses rapidly and, similar to rampant caries, can progress rapidly to dentin (<xref ref-type="bibr" rid="B90">90</xref>). <italic>Lactobacillus</italic> has a high affinity for dentin collagen (<xref ref-type="bibr" rid="B91">91</xref>&#x2013;<xref ref-type="bibr" rid="B93">93</xref>). We speculate that this may be the reason why more lactobacilli tend to be detected at ECC lesion sites.</p>
<table-wrap id="T8" position="float"><label>Table 8</label>
<caption><p>Research on ECC and <italic>Lactobacillus.</italic></p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Topic</th>
<th valign="top" align="center">Author, year</th>
<th valign="top" align="center">Subject</th>
<th valign="top" align="center">Species</th>
<th valign="top" align="center">Main conclusions</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" rowspan="8">The load and species of Lactobacillus at ECC carious sites.</td>
<td valign="top" align="center">Leme et al. 2022 (<xref ref-type="bibr" rid="B80">80</xref>)</td>
<td valign="top">Preschoolers</td>
<td valign="top">&#x2013;</td>
<td valign="top"><italic>L. acidophilus</italic> and <italic>L. gasseri</italic> was associated with ECC in children with normal nutritional status.</td>
</tr>
<tr>
<td valign="top">Indiani et al. 2020 (<xref ref-type="bibr" rid="B81">81</xref>)</td>
<td valign="top">Preschoolers with or without ECC</td>
<td valign="top">&#x2013;</td>
<td valign="top"><italic>S. mutans</italic> and <italic>Lactobacillus</italic> levels in the mouth and gut are linked to ECC, with obesity influencing this connection.</td>
</tr>
<tr>
<td valign="top">Reis et al. 2021 (<xref ref-type="bibr" rid="B82">82</xref>)</td>
<td valign="top">Children between 2 and 5 years of age with dentinal lesion</td>
<td valign="top">&#x2013;</td>
<td valign="top">The abundant presence of <italic>L. casei</italic> species in active dentinal caries lesions indicates their potential link to caries activity, with the wzb gene possibly playing a key role in caries progression.</td>
</tr>
<tr>
<td valign="top">Liu et al. 2019 (<xref ref-type="bibr" rid="B83">83</xref>)</td>
<td valign="top">Children from 3 to 6 years of age with ECC</td>
<td valign="top">&#x2013;</td>
<td valign="top">A higher salivary level of LB was observed in children with more severe caries, although the difference was not statistically significant.</td>
</tr>
<tr>
<td valign="top">Klinke et al. 2014 (<xref ref-type="bibr" rid="B84">84</xref>)</td>
<td valign="top">Infants with ECC</td>
<td valign="top">&#x2013;</td>
<td valign="top">The removal and restoration of ECC lesions under general anesthesia effectively reduced cariogenic bacteria and yeasts.</td>
</tr>
<tr>
<td valign="top">Ramamurthy et al. 2014 (<xref ref-type="bibr" rid="B85">85</xref>)</td>
<td valign="top">Children aged 2&#x2013;5 years with or without S-ECC</td>
<td valign="top">&#x2013;</td>
<td valign="top">s-ECC is positively associated with higher salivary levels of both MS and LB in preschool children from low socioeconomic backgrounds.</td>
</tr>
<tr>
<td valign="top">Mitrakul et al. 2017 (<xref ref-type="bibr" rid="B86">86</xref>)</td>
<td valign="top">Children with S-ECC and caries-free</td>
<td valign="top">&#x2013;</td>
<td valign="top">The levels of <italic>S. mutans</italic>, Lactobacillus, bifidobacterium, and their ratio to total bacteria were notably higher in both initial and mature dental plaques of children with S-ECC.</td>
</tr>
<tr>
<td valign="top">Indiani et al. 2020 (<xref ref-type="bibr" rid="B81">81</xref>)</td>
<td valign="top">Preschoolers with or without ECC</td>
<td valign="top">&#x2013;</td>
<td valign="top">The levels of <italic>S. mutans</italic> and the presence of <italic>Lactobacillus</italic> in both the oral cavity and lower gastrointestinal tract were linked to ECC.</td>
</tr>
<tr>
<td valign="top" align="left" rowspan="6">Studies on Lactobacillus-Based Therapies for ECC</td>
<td valign="top">Staszczyk et al. 2022 (<xref ref-type="bibr" rid="B69">69</xref>)</td>
<td valign="top">Children aged 3&#x2013;6 years with or without ECC</td>
<td valign="top"><italic>L. salivarius</italic></td>
<td valign="top">Frequent short-term consumption of probiotics may help decrease the incidence of dental caries.</td>
</tr>
<tr>
<td valign="top">Hassl&#x00F6;f et al. 2013 (<xref ref-type="bibr" rid="B87">87</xref>)</td>
<td valign="top">Infants aged 4 months</td>
<td valign="top"><italic>L. paracasei F19</italic></td>
<td valign="top">Early intervention with the probiotic <italic>L. paracasei F19</italic> does not have a long-term impact on caries experience.</td>
</tr>
<tr>
<td valign="top">Pahumunto et al. 2018 (<xref ref-type="bibr" rid="B39">39</xref>)</td>
<td valign="top">Children, aged 1.5&#x2013;5 years old</td>
<td valign="top"><italic>L. paracasei SD1</italic></td>
<td valign="top">Consumption of milk powder containing <italic>L. paracasei SD1</italic> led to a reduction in salivary <italic>S. mutans</italic> levels and delayed the development of new caries.</td>
</tr>
<tr>
<td valign="top">Zeng et al. 2023 (<xref ref-type="bibr" rid="B34">34</xref>)</td>
<td valign="top"><italic>S. mutans</italic> and <italic>C. albicans</italic> Clinical isolates from Children with ECC</td>
<td valign="top"><italic>L. plantarum 14917</italic></td>
<td valign="top"><italic>L. plantarum 14917</italic> showed significant inhibition against clinical isolates of <italic>S. mutans</italic> and <italic>C. albicans.</italic></td>
</tr>
<tr>
<td valign="top">Krzy&#x015B;ciak et al. 2017 (<xref ref-type="bibr" rid="B88">88</xref>)</td>
<td valign="top"><italic>S. mutans</italic> and <italic>C. albicans</italic> clinical strains, isolated from dental plaque of patients with ECC</td>
<td valign="top"><italic>L. salivarius</italic></td>
<td valign="top"><italic>L. salivarius</italic> may secrete intermediates that inhibit the biofilm formation of <italic>S. mutans</italic> and <italic>C. albicans</italic>.</td>
</tr>
<tr>
<td valign="top">Plonka et al. 2012 (<xref ref-type="bibr" rid="B89">89</xref>)</td>
<td valign="top">Infants</td>
<td valign="top">&#x2013;</td>
<td valign="top">The period between 6 and 12 months is a critical window during which key factors can be managed to reduce the colonization of LB.</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn3"><p>ECC, early childhood caries; S-ECC, severe early childhood caries; LB, lactobacilli; MS, mutans streptococci.</p></fn>
</table-wrap-foot>
</table-wrap>
<p>This study is founded on a bibliometric analysis of the included studies, which inherently possesses several limitations. Firstly, there exists the potential for publication bias. Although the utilization of the WoSCC database contributes to ensuring the credibility and authority of the included data, it might also constrain the comprehensiveness of the information. Additionally, the publications selected for the bibliometric analysis were initially identified through pre-searching with a predefined search formula and then manually filtered. However, the process of data exportation and filtering might result in data loss, misidentification of articles, or other problems. Moreover, analysis software VOSviewer still has scope for improvement. For instance, synonymous entities, such as authors, institutions, and keywords, might fail to be precisely identified or discriminated, giving rise to circumstances where the same institution, author, or synonym is not accurately merged. Furthermore, only English-language studies were encompassed within this analysis, which could have resulted in an underrepresentation of research capabilities from non-English-speaking countries.</p>
</sec>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability"><title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.</p>
</sec>
<sec id="s7" sec-type="author-contributions"><title>Author contributions</title>
<p>DF: Conceptualization, Data curation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. XS: Data curation, Formal Analysis, Project administration, Validation, Visualization, Writing &#x2013; review &#x0026; editing. LY: Data curation, Writing &#x2013; original draft, Formal Analysis. GZ: Writing &#x2013; review &#x0026; editing. MJ: Data curation, Supervision, Writing &#x2013; review &#x0026; editing. GL: Methodology, Supervision, Writing &#x2013; review &#x0026; editing. YZ: Supervision, Writing &#x2013; review &#x0026; editing. LZ: Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec id="s8" sec-type="funding-information"><title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grant from the National Natural Science Foundation of China (grant no. 82071111).</p>
</sec>
<sec id="s9" sec-type="COI-statement"><title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s11" sec-type="ai-statement"><title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec id="s10" sec-type="disclaimer"><title>Publisher&#x0027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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