[en] [en] OBJECTIVES: This randomized, double-blind, placebo-controlled clinical trial evaluated the effect of L. reuteri administration on postsurgical wound healing, pain levels, and patient-reported outcomes (PROs) following extraction of fully impacted teeth.
METHODS: Consecutive patients requiring surgical extractions were included and randomly allocated to either test (probiotic) or control group (placebo). Following oral hygiene procedures, patients began a daily probiotic/placebo intake 7 days before surgery until 14 days after surgery. Follow-up was performed at 3 (T3), 7 (T7), and 14 (T14) days postop. Wound healing, postoperative complications, pain, perceived functional impairment, and Oral Health Impact Profile-14 (OHIP-14) were registered.
RESULTS: A total of 128 patients (67 in the test group and 61 in the control group) were analyzed. Wound healing significantly improved in the test group at T3 and T7. Trismus was significantly milder in the test group at T3 and T14. No differences in pain were noted. The test group experienced reduced chewing impairment and difficulty in oral hygiene procedures, exhibited significantly lower scores of OHIP-14 at T14, and required a reduced number of anti-inflammatory medications in the first 7 days.
CONCLUSIONS: Limosilactobacillus reuteri administration improved wound healing, reduced the severity of trismus, and was associated with improved PROs following impacted tooth extractions.
TRIAL REGISTRATION: The study protocol was registered in a clinical trials database (Clinicaltrials.gov) with registration number NCT04903925.
Disciplines :
Dentistry & oral medicine
Author, co-author :
Cinquini, Chiara ; Université de Liège - ULiège > Dental biomaterials research unit (d-BRU) ; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Izzetti, Rossana; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Nisi, Marco ; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Gulia, Francesco; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Garcia Mira, Berta; Department of Stomatology, University of Valencia, Valencia, Spain
Barone, Antonio; Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
Bădăluță, V. A., C. Curuțiu, L. M. Dițu, A. M. Holban, and V. Lazăr. 2024. “Probiotics in Wound Healing.” International Journal of Molecular Sciences 25: 5723.
Banjonjit, S., M. Taweechotipatr, and S. Rungsiyanont. 2022. “Effect of Probiotic Lactobacillus paracasei on Tumor Necrosis Factor-Alpha Level in Gingival Crevicular Fluid of Patients Undergoing Impacted Third Molar Removal.” Journal of Oral Science 64: 21–0457.
Borges, A. H., F. L. M. Pedro, M. C. Bandéca, et al. 2014. “Prevalence of Impacted Teeth in a Brazilian Subpopulation.” Journal of Contemporary Dental Practice 15: 209–213.
Boyanova, L., and I. Mitov. 2012. “Coadministration of Probiotics With Antibiotics: Why, When and for How Long?” Expert Review of Anti-Infective Therapy 10: 407–409.
Cinquini, C., S. Marchionni, G. Derchi, M. Miccoli, M. Gabriele, and A. Barone. 2021. “Non-Impacted Tooth Extractions and Antibiotic Treatment: A RCT Study.” Oral Diseases 27: 1042–1051.
Crobach, M. J. T., J. J. Vernon, V. G. Loo, et al. 2018. “Understanding Clostridium difficile Colonization.” Clinical Microbiology Reviews 31: 10–1128.
Cuschieri, S. 2019. “The CONSORT Statement.” Saudi Journal of Anesthesia 13: 27.
da Silva Menezes, C. G., S. C. Sartoretto, R. S. Louro, J. B. de Moraes, and V. Moraschini. 2024. “Prevalence of Impacted Teeth: A Radiographical Retrospective Rio de Janeiro Population-Based Study.” Journal of Oral and Maxillofacial Surgery 23: 75–80.
Dylag, K., M. Hubalewska-Mazgaj, M. Surmiak, J. Szmyd, and T. Brzozowski. 2014. “Probiotics in the Mechanism of Protection Against Gut Inflammation and Therapy of Gastrointestinal Disorders.” Current Pharmaceutical Design 20: 1149–1155.
Elavarasu, S., P. Jayapalan, and T. Murugan. 2012. “Bugs That Debugs: Probiotics.” Journal of Pharmacy & Bioallied Sciences 4: S319–S322.
Ettinger, G., K. MacDonald, G. Reid, and J. P. Burton. 2014. “The Influence of the Human Microbiome and Probiotics on Cardiovascular Health.” Gut Microbes 5: 719–728.
Fernandes, M. J., D. A. Ruta, G. R. Ogden, N. B. Pitts, and S. A. Ogston. 2006. “Assessing Oral Health-Related Quality of Life in General Dental Practice in Scotland: Validation of the OHIP-14.” Community Dentistry and Oral Epidemiology 34: 53–62.
Ferrés-Amat, E., J. Espadaler-Mazo, J. L. Calvo-Guirado, et al. 2020. “Probiotics Diminish the Post-Operatory Pain Following Mandibular Third Molar Extraction: A Randomised Double-Blind Controlled Trial (Pilot Study).” Beneficial Microbes 11: 631–640.
Food and Agriculture Organization of the United Nations. 2002. “Probiotics in Food: Health and Nutritional Properties and Guidelines for Evaluation.”
Ghaeminia, H., M. E. L. Nienhuijs, V. Toedtling, et al. 2020. “Surgical Removal Versus Retention for the Management of Asymptomatic Disease-Free Impacted Wisdom Teeth.” Cochrane Database of Systematic Reviews 5, no. 5: CD003879. https://doi.org/10.1002/14651858.
Gilbert, J. A., M. J. Blaser, J. G. Caporaso, J. K. Jansson, S. V. Lynch, and R. Knight. 2018. “Current Understanding of the Human Microbiome.” Nature Medicine 24: 392–400.
Gruner, D., S. Paris, and F. Schwendicke. 2016. “Probiotics for Managing Caries and Periodontitis: Systematic Review and Meta-Analysis.” Journal of Dentistry 48: 16–25.
Güngör, Ö. E., Z. Kırzıoğlu, E. Dinçer, and M. Kıvanç. 2013. “Who Will Win the Race in Childrens’ Oral Cavities? Streptococcus mutans or Beneficial Lactic Acid Bacteria?” Beneficial Microbes 4: 237–246.
Gurtner, G. C., S. Werner, Y. Barrandon, and M. T. Longaker. 2008. “Wound Repair and Regeneration.” Nature 453: 314–321.
Human Microbiome Project Consortium. 2012. “Structure, Function and Diversity of the Healthy Human Microbiome.” Nature 486: 207–214.
Huseini, H. F., G. Rahimzadeh, M. R. Fazeli, M. Mehrazma, and M. Salehi. 2012. “Evaluation of Wound Healing Activities of Kefir Products.” Burns 38: 719–723.
Iglesias-Martin, F., A. Garcia-Perla-Garcia, R. Yanez-Vico, et al. 2014. “Comparative Trial Between the Use of Amoxicillin and Amoxicillin Clavulanate in the Removal of Third Molars.” Medicina Oral, Patología Oral y Cirugía Bucal 19: e612–e615.
Invernici, M. M., S. L. Salvador, P. H. F. Silva, et al. 2018. “Effects of Bifidobacterium Probiotic on the Treatment of Chronic Periodontitis: A Randomized Clinical Trial.” Journal of Clinical Periodontology 45: 1198–1210.
Jeong, D., D.-H. Kim, K.-Y. Song, and K.-H. Seo. 2018. “Antimicrobial and Anti-Biofilm Activities of Lactobacillus kefiranofaciens DD2 Against Oral Pathogens.” Journal of Oral Microbiology 10: 1472985.
Jones, S. E., and J. Versalovic. 2009. “Probiotic Lactobacillus reuteri Biofilms Produce Antimicrobial and Anti-Inflammatory Factors.” BMC Microbiology 9: 35.
Jørgensen, M. R., P. Abrahamsson, D.-Å. Wälivaara, and S. Twetman. 2022. “Probiotic Supplements and Postoperative Complications After Tooth Extractions and Third Molar Surgery: A Systematic Review.” Minerva Dental and Oral Science 71: 242–247.
Kekkonen, R. A., E. Kajasto, M. Miettinen, V. Veckman, R. Korpela, and I. Julkunen. 2008. “Probiotic Leuconostoc mesenteroides Ssp. Cremoris and Streptococcus thermophilus Induce IL-12 and IFN-γ Production.” World Journal of Gastroenterology 14: 1192–1203.
Kiousi, D. E., C. Efstathiou, V. Tzampazlis, et al. 2023. “Genetic and Phenotypic Assessment of the Antimicrobial Activity of Three Potential Probiotic Lactobacilli Against Human Enteropathogenic Bacteria.” Frontiers in Cellular and Infection Microbiology 13: 1127256.
Krasse, P., B. Carlsson, C. Dahl, A. Paulsson, A. Nilsson, and G. Sinkiewicz. 2006. “Decreased Gum Bleeding and Reduced Gingivitis by the Probiotic Lactobacillus reuteri.” Swedish Dental Journal 30: 55–60.
Langman, M. J. S., J. Weil, P. Wainwright, et al. 1994. “Risks of Bleeding Peptic Ulcer Associated With Individual Non-Steroidal Anti-Inflammatory Drugs.” Lancet 343: 1075–1078.
Lukic, J., V. Chen, I. Strahinic, et al. 2017. “Probiotics or Pro-Healers: The Role of Beneficial Bacteria in Tissue Repair.” Wound Repair and Regeneration 25: 912–922.
Mullish, B. H., D. R. Michael, T. S. Webberley, et al. 2023. “The Gastrointestinal Status of Healthy Adults: A Post Hoc Assessment of the Impact of Three Distinct Probiotics.” Beneficial Microbes 14: 183–195.
Nes, I. F., D. B. Diep, L. S. Hvarstein, M. B. Brurberg, V. Eijsink, and H. Holo. 1996. “Biosynthesis of Bacteriocins in Lactic Acid Bacteria.” Antonie Van Leeuwenhoek 70: 113–128.
Neut, C., S. Mahieux, and L. J. Dubreuil. 2017. “Antibiotic Susceptibility of Probiotic Strains: Is It Reasonable to Combine Probiotics With Antibiotics?” Médecine et Maladies Infectieuses 47: 477–483.
Ogunrinola, G. A., J. O. Oyewale, O. O. Oshamika, and G. I. Olasehinde. 2020. “The Human Microbiome and Its Impacts on Health.” International Journal of Microbiology 2020: 1–7.
Romani Vestman, N., T. Chen, P. Lif Holgerson, C. Öhman, and I. Johansson. 2015. “Oral Microbiota Shift After 12-Week Supplementation With Lactobacillus reuteri DSM 17938 and PTA 5289; A Randomized Control Trial.” PLoS One 10: e0125812.
Slade, G. D. 1997. “Derivation and Validation of a Short-Form Oral Health Impact Profile.” Community Dentistry and Oral Epidemiology 25: 284–290.
Staab, B., S. Eick, G. Knöfler, and H. Jentsch. 2009. “The Influence of a Probiotic Milk Drink on the Development of Gingivitis: A Pilot Study.” Journal of Clinical Periodontology 36: 850–856.
Togo, C., A. P. Zidorio, V. Gonçalves, P. Botelho, K. de Carvalho, and E. Dutra. 2021. “Does Probiotic Consumption Enhance Wound Healing? A Systematic Review.” Nutrients 14: 111.
Turnbaugh, P. J., R. E. Ley, M. Hamady, C. M. Fraser-Liggett, R. Knight, and J. I. Gordon. 2007. “The Human Microbiome Project.” Nature 449: 804–810.
Twetman, S., B. Derawi, M. Keller, K. Ekstrand, T. Yucel-Lindberg, and C. Stecksén-Blicks. 2009. “Short-Term Effect of Chewing Gums Containing Probiotic Lactobacillus reuteri on the Levels of Inflammatory Mediators in Gingival Crevicular Fluid.” Acta Odontologica Scandinavica 67: 19–24.
Twetman, S., and M. R. Jørgensen. 2021. “Can Probiotic Supplements Prevent Early Childhood Caries? A Systematic Review and Meta-Analysis.” Beneficial Microbes 12: 231–238.
Twetman, S., M. R. Jørgensen, and M. K. Keller. 2017. “Fifteen Years of Probiotic Therapy in the Dental Context: What Has Been Achieved?” Journal of the California Dental Association 45: 539–545.
Twetman, S., M. K. Keller, L. Lee, T. Yucel-Lindberg, and A. M. L. Pedersen. 2018. “Effect of Probiotic Lozenges Containing Lactobacillus reuteri on Oral Wound Healing: A Pilot Study.” Beneficial Microbes 9: 691–696.
Varghese, G. 2021. “Management of Impacted Third Molars.” In Oral and Maxillofacial Surgery for the Clinician, 299–328. Springer Nature Singapore.
Vivekananda, M. R., K. L. Vandana, and K. G. Bhat. 2010. “Effect of the Probiotic Lactobacilli reuteri (Prodentis) in the Management of Periodontal Disease: A Preliminary Randomized Clinical Trial.” Journal of Oral Microbiology 2: 5344.
Wachtel, H., G. Schenk, S. Böhm, D. Weng, O. Zuhr, and M. B. Hürzeler. 2003. “Microsurgical Access Flap and Enamel Matrix Derivative for the Treatment of Periodontal Intrabony Defects: A Controlled Clinical Study.” Journal of Clinical Periodontology 30: 496–504.
Wälivaara, D.-Å., I. Sjögren, N. Gerasimcik, T. Yucel-Lindberg, S. Twetman, and P. Abrahamsson. 2019. “Effects of Lactobacillus reuteri-Containing Lozenges on Healing After Surgical Removal of Mandibular Third Molars: A Randomised Controlled Trial.” Beneficial Microbes 10: 653–659.
Walker, W. A. 2008. “Mechanisms of Action of Probiotics.” Clinical Infectious Diseases 46: S87–S91.
World Medical Association Declaration of Helsinki. 2013. “World Medical Association Declaration of Helsinki.” JAMA 310: 2191.
Yamada, N., K. Kobayashi, A. Nagira, et al. 2024. “The Beneficial Effects of Regular Intake of Lactobacillus Paragasseri OLL2716 on Gastric Discomfort in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study.” Nutrients 16: 3188.
