{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:29:31Z","timestamp":1784809771617,"version":"3.55.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460189"],"award-info":[{"award-number":["82460189"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Dental caries is driven by dysbiosis of oral biofilms. Conventional antibiotics easily disrupt oral commensal balance, creating an urgent need for natural, non-antibiotic agents that can target cariogenic biofilms without causing ecological collapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The antimicrobial and antibiofilm efficacy of Naringin was evaluated\n                      <jats:italic>in vitro<\/jats:italic>\n                      against planktonic and biofilm states of\n                      <jats:italic>Streptococcus mutans, Streptococcus sobrinus, Streptococcus sanguinis<\/jats:italic>\n                      (mono-species), and their multi-species consortium. Minimum inhibitory\/bactericidal concentrations (MIC\/MBC) and minimum biofilm inhibitory\/reduction concentrations (MBIC\/MBRC) were determined. Effects on acid production, extracellular polysaccharide (EPS) synthesis, and bacterial adhesion to hydroxyapatite (HAP) were mechanistically investigated.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a rat caries model induced by the multi-species consortium was topically treated with Naringin (2 \u00d7 MIC, MIC, 1\/2 \u00d7 MIC) for 4 weeks. Caries lesions were evaluated using Keyes scoring and micro-computed tomography. Oral microbiota, serum biochemistry, and histopathology were analyzed for safety assessment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Naringin exhibited potent, concentration-dependent antimicrobial activity. MICs were 1.00 mg\/mL for\n                      <jats:italic>S. mutans<\/jats:italic>\n                      and\n                      <jats:italic>S. sanguinis<\/jats:italic>\n                      , 0.50 mg\/mL for\n                      <jats:italic>S. sobrinus<\/jats:italic>\n                      , and 0.50 mg\/mL for the multi-species consortium. Naringin at MBIC (2 mg\/mL for multi-species) significantly disrupted biofilm architecture, reduced viable bacteria, and inhibited EPS synthesis. It maintained biofilm pH above 5.5 (the critical threshold for enamel demineralization), inhibited lactate production, and reduced multi-species bacterial adhesion to HAP by 68.3% at MIC.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , Naringin (MIC) significantly reduced Keyes scores on smooth and sulcal surfaces by over 60%, preserved enamel integrity, and rebalanced the oral microbiota without inducing mucosal irritation or systemic toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Naringin, a natural non-antibiotic agent, effectively inhibits the \u201cadhesion-biofilm-acid-EPS\u201d cascade of multi-species cariogenic biofilms. Its selective efficacy against pathogens and favorable\n                      <jats:italic>in vivo<\/jats:italic>\n                      safety profile position it as a promising ecological agent for caries prevention by addressing oral dysbiosis at its root.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1722083","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T06:47:53Z","timestamp":1765349273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Naringin as a non-antibiotic agent for multi-species oral biofilm control: in vitro antimicrobial mechanisms and in vivo safety in a rat caries model"],"prefix":"10.3389","volume":"16","author":[{"given":"Jie","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizinigaer","family":"Yasen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/S0140-6736(24)02811-3","article-title":"Trends in the global, regional, and national burden of oral conditions from 1990 to 2021: A systematic analysis for the Global Burden of Disease Study 2021.","volume":"405","author":"Bernabe","year":"2025","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"127548","DOI":"10.1016\/j.micres.2023.127548","article-title":"Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges.","volume":"279","author":"Cao","year":"2024","journal-title":"Microbiol. 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