Influence of probiotics on the periodontium, the oral microbiota and the immune response during orthodontic treatment in adolescent and adult patients (ProMB Trial): study protocol for a prospective, double-blind, controlled, randomized clinical trial

Corinna L Seidel, Roman G Gerlach, Matthias Weider, Theresa Wölfel, Vincent Schwarz, Armin Ströbel, Helga Schmetzer, Christian Bogdan, Lina Gölz, Corinna L Seidel, Roman G Gerlach, Matthias Weider, Theresa Wölfel, Vincent Schwarz, Armin Ströbel, Helga Schmetzer, Christian Bogdan, Lina Gölz

Abstract

Background: Orthodontic treatment with fixed appliances is often necessary to correct malocclusions in adolescence or adulthood. However, oral hygiene is complicated by appliances, and prior studies indicate that they may trigger oral inflammation and dysbiosis of the oral microbiota, especially during the first 3 months after insertion, and, thus, may present a risk for inflammatory oral diseases. In recent periodontal therapeutic studies, probiotics have been applied to improve clinical parameters and reduce local inflammation. However, limited knowledge exists concerning the effects of probiotics in orthodontics. Therefore, the aim of our study is to evaluate the impact of probiotics during orthodontic treatment.

Methods: This study is a monocentric, randomized, double blind, controlled clinical study to investigate the effectiveness of daily adjuvant use of Limosilactobacillus reuteri (Prodentis®-lozenges, DSM 17938, ATCC PTA 5289) versus control lozenges during the first three months of orthodontic treatment with fixed appliances. Following power analysis, a total of 34 adolescent patients (age 12-17) and 34 adult patients (18 years and older) undergoing orthodontic treatment at the University Hospital Erlangen will be assigned into 2 parallel groups using a randomization plan for each age group. The primary outcome measure is the change of the gingival index after 4 weeks. Secondary outcomes include the probing pocket depth, the modified plaque index, the composition of the oral microbiota, the local cytokine expression and-only for adults-serum cytokine levels and the frequencies of cells of the innate and adaptive immune system in peripheral blood.

Discussion: Preventive strategies in everyday orthodontic practice include oral hygiene instructions and regular dental cleaning. Innovative methods, like adjuvant use of oral probiotics, are missing. The aim of this study is to analyse, whether probiotics can improve clinical parameters, reduce inflammation and prevent dysbiosis of the oral microbiota during orthodontic treatment. If successful, this study will provide the basis for a new strategy of prophylaxis of oral dysbiosis-related diseases during treatment with fixed appliances.

Trial registration: This trial is registered at ClinicalTrials.gov in two parts under the number NCT04598633 (Adolescents, registration date 10/22/2020), and NCT04606186 (Adults, registration date 10/28/2020).

Keywords: Cytokines; Inflammation; Lactobacillus reuteri; Limosilactobacillus reuteri; Oral health; Oral microbiota; Orthodontic treatment; Prevention; Probiotics; Study protocol.

Conflict of interest statement

The company BioGaia AB provides non-financial support by supply of the Limosilactobacillus reuteri Prodentis®-lozenges (DSM 17938, ATCC PTA 5289) and control lozenges. The design, management, analyses, reporting of the study, interpretation of data and the decision to submit results are entirely independent of the non-financial supporter.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Trial protocol flow chart. n = number; *for the patient and/or legal guardian
Fig. 2
Fig. 2
A time line showing all five study time points is given. Base line (T0) = before the insertion of the fixed appliance; T1 =  ~ one week (w) after insertion of fixed appliance/ start of lozenge intake; T2 =  ~ four w after insertion of fixed appliance/ start of lozenge intake; T3 =  ~ 12w after insertion of the fixed appliance = last day of lozenge intake; T4 =  ~ 24w after insertion of fixed appliance = 24w after start of lozenge intake = 12w after end of lozenge intake

References

    1. Khandakji MN, Ghafari JG. Evaluation of commonly used occlusal indices in determining orthodontic treatment need. Eur J Orthod. 2020;42(1):107–114. doi: 10.1093/ejo/cjz042.
    1. Brook PH, Shaw WC. The development of an index of orthodontic treatment priority. Eur J Orthod. 1989;11(3):309–320. doi: 10.1093/oxfordjournals.ejo.a035999.
    1. Verrusio C, Iorio-Siciliano V, Blasi A, Leuci S, Adamo D, Nicolò M. The effect of orthodontic treatment on periodontal tissue inflammation: a systematic review. Quintessence Int. 2018;49(1):69–77. doi: 10.3290/j.qi.a39225.
    1. Alrashed M, Alqerban A. The relationship between malocclusion and oral health-related quality of life among adolescents: a systematic literature review and meta-analysis. Eur J Orthod. 2021;43(2):173–183. doi: 10.1093/ejo/cjaa051.
    1. Antezack A, Monnet-Corti V. Oral and periodontal hygiene in orthodontic patients. Orthod Fr. 2018;89(2):181–190. doi: 10.1051/orthodfr/2018015.
    1. Jepsen S, Kebschull M, Deschner J. Relationship between periodontitis and systemic diseases. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2011;54(9):1089–1096. doi: 10.1007/s00103-011-1348-4.
    1. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30–44. doi: 10.1038/nri3785.
    1. Deschner J, Haak T, Jepsen S, Kocher T, Mehnert H, Meyle J, Schumm-Draeger PM, Tschöpe D. Diabetes mellitus and periodontitis, Bidirectional relationship and clinical implications. A consensus document. Internist (Berl) 2011;52(4):466–477. doi: 10.1007/s00108-011-2835-2.
    1. Kebschull M, Demmer RT, Papapanou PN. "Gum bug, leave my heart alone!"—epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res. 2010;89(9):879–902. doi: 10.1177/0022034510375281.
    1. Mougeot JC, Stevens CB, Paster BJ, Brennan MT, Lockhart PB, Mougeot FK. Porphyromonas gingivalis is the most abundant species detected in coronary and femoral arteries. J Oral Microbiol. 2017;9(1):1281562. doi: 10.1080/20002297.2017.1281562.
    1. Mei F, Xie M, Huang X, Long Y, Lu X, Wang X, Chen L. Porphyromonas gingivalis and its systemic impact: current status. Pathogens. 2020;9(11):5. doi: 10.3390/pathogens9110944.
    1. Yang J, Wu J, Liu Y, Huang J, Lu Z, Xie L, Sun W, Ji Y. Porphyromonas gingivalis infection reduces regulatory T cells in infected atherosclerosis patients. PLoS ONE. 2014;9(1):e86599. doi: 10.1371/journal.pone.0086599.
    1. Yang J, Wu J, Zhang R, Yao M, Liu Y, Miao L, Sun W. Porphyromonas gingivalis oral infection promote T helper 17/Treg imbalance in the development of atherosclerosis. J Dent Sci. 2017;12(1):60–69. doi: 10.1016/j.jds.2016.10.003.
    1. Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, Nguyen M, Haditsch U, Raha D, Griffin C, et al. Porphyromonas gingivalis in Alzheimer's disease brains: evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333. doi: 10.1126/sciadv.aau3333.
    1. Maresz KJ, Hellvard A, Sroka A, Adamowicz K, Bielecka E, Koziel J, Gawron K, Mizgalska D, Marcinska KA, Benedyk M, et al. Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD) PLoS Pathog. 2013;9(9):e1003627. doi: 10.1371/journal.ppat.1003627.
    1. Blasco-Baque V, Garidou L, Pomié C, Escoula Q, Loubieres P, Le Gall-David S, Lemaitre M, Nicolas S, Klopp P, Waget A, et al. Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response. Gut. 2017;66(5):872–885. doi: 10.1136/gutjnl-2015-309897.
    1. Schenkein HA, Bradley JL, Purkall DB. Anticardiolipin in porphyromonas gingivalis antisera causes fetal loss in mice. J Dent Res. 2013;92(9):814–818. doi: 10.1177/0022034513497959.
    1. Vander Haar EL, So J, Gyamfi-Bannerman C, Han YW. Fusobacterium nucleatum and adverse pregnancy outcomes: epidemiological and mechanistic evidence. Anaerobe. 2018;50:55–59. doi: 10.1016/j.anaerobe.2018.01.008.
    1. Krishnan V, Davidovitch Z. On a path to unfolding the biological mechanisms of orthodontic tooth movement. J Dent Res. 2009;88(7):597–608. doi: 10.1177/0022034509338914.
    1. Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofac Orthop. 2006;129(4):469.e461–432. doi: 10.1016/j.ajodo.2005.10.007.
    1. Yucel-Lindberg T, Bage T. Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med. 2013;15:e7. doi: 10.1017/erm.2013.8.
    1. Barros SP, Williams R, Offenbacher S, Morelli T. Gingival crevicular fluid as a source of biomarkers for periodontitis. Periodontol. 2016;70(1):53–64. doi: 10.1111/prd.12107.
    1. Tsuchida S, Satoh M, Takiwaki M, Nomura F. Current status of proteomic technologies for discovering and identifying gingival crevicular fluid biomarkers for periodontal disease. Int J Mol Sci. 2018;20(1):86. doi: 10.3390/ijms20010086.
    1. Delima AJ, Karatzas S, Amar S, Graves DT. Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. J Infect Dis. 2002;186(4):511–516. doi: 10.1086/341778.
    1. Thunell DH, Tymkiw KD, Johnson GK, Joly S, Burnell KK, Cavanaugh JE, Brogden KA, Guthmiller JM. A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. J Periodontal Res. 2010;45(1):148–152. doi: 10.1111/j.1600-0765.2009.01204.x.
    1. Holmlund A, Hänström L, Lerner UH. Bone resorbing activity and cytokine levels in gingival crevicular fluid before and after treatment of periodontal disease. J Clin Periodontol. 2004;31(6):475–482. doi: 10.1111/j.1600-051X.2004.00504.x.
    1. Syrjäläinen S, Gursoy UK, Gursoy M, Pussinen P, Pietiäinen M, Jula A, Salomaa V, Jousilahti P, Könönen E. Salivary cytokine biomarker concentrations in relation to obesity and periodontitis. J Clin Med. 2019 doi: 10.3390/jcm8122152.
    1. Kirschneck C, Fanghanel J, Wahlmann U, Wolf M, Roldan JC, Proff P. Interactive effects of periodontitis and orthodontic tooth movement on dental root resorption, tooth movement velocity and alveolar bone loss in a rat model. Ann Anat. 2017;210:32–43. doi: 10.1016/j.aanat.2016.10.004.
    1. Ahuja R, Almuzian M, Khan A, Pascovici D, Dalci O, Darendeliler MA. A preliminary investigation of short-term cytokine expression in gingival crevicular fluid secondary to high-level orthodontic forces and the associated root resorption: case series analytical study. Prog Orthod. 2017;18(1):23. doi: 10.1186/s40510-017-0177-x.
    1. Tarallo F, Chimenti C, Paiella G, Cordaro M, Tepedino M. Biomarkers in the gingival crevicular fluid used to detect root resorption in patients undergoing orthodontic treatment: a systematic review. Orthod Craniofac Res. 2019 doi: 10.1111/ocr.12329.
    1. Papageorgiou SN, Xavier GM, Cobourne MT, Eliades T. Effect of orthodontic treatment on the subgingival microbiota: a systematic review and meta-analysis. Orthod Craniofac Res. 2018;21(4):175–185. doi: 10.1111/ocr.12237.
    1. Guo R, Lin Y, Zheng Y, Li W. The microbial changes in subgingival plaques of orthodontic patients: a systematic review and meta-analysis of clinical trials. BMC Oral Health. 2017;17(1):90. doi: 10.1186/s12903-017-0378-1.
    1. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, Lakshmanan A, Wade WG. The human oral microbiome. J Bacteriol. 2010;192(19):5002–5017. doi: 10.1128/jb.00542-10.
    1. The Human Oral Microbiome Database: a web accessible resource for investigating oral microbe taxonomic and genomic information. Database J Biol Database Curat 2010; 2010:baq013. 10.1093/database/baq013.
    1. Costello E. The application of ecological theory toward an understanding of the human microbiome. Science. 2012;336(6086):1255–1262. doi: 10.1126/science.1224203.
    1. Jordan RA, Bodechtel C, Hertrampf K, Hoffmann T, Kocher T, Nitschke I, Schiffner U, Stark H, Zimmer S, Micheelis W, et al. The Fifth German Oral Health Study (Fünfte Deutsche Mundgesundheitsstudie, DMS V) - rationale, design, and methods. BMC Oral Health. 2014;14:161–161. doi: 10.1186/1472-6831-14-161.
    1. Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics—approaching a definition. Am J Clin Nutr. 2001;73(2 Suppl):361s–364s. doi: 10.1093/ajcn/73.2.361s.
    1. de Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol. 2008;111:1–66. doi: 10.1007/10_2008_097.
    1. Jentsch H. Probiotika im Rahmen der antiinfektiösen Therapie der Parodontitis. Wissen kompakt. 2018;12(3):139–147. doi: 10.1007/s11838-018-0065-3.
    1. Yan F, Polk DB. Probiotics: progress toward novel therapies for intestinal diseases. Curr Opin Gastroenterol. 2010;26(2):95–101. doi: 10.1097/MOG.0b013e328335239a.
    1. Borchers AT, Selmi C, Meyers FJ, Keen CL, Gershwin ME. Probiotics and immunity. J Gastroenterol. 2009;44(1):26–46. doi: 10.1007/s00535-008-2296-0.
    1. Borchers AT, Keen CL, Gershwin ME. The influence of yogurt/Lactobacillus on the innate and acquired immune response. Clin Rev Allergy Immunol. 2002;22(3):207–230. doi: 10.1007/s12016-002-0009-7.
    1. Giorgetti G, Brandimarte G, Fabiocchi F, Ricci S, Flamini P, Sandri G, Trotta MC, Elisei W, Penna A, Lecca PG, et al. Interactions between innate immunity, microbiota, and probiotics. J Immunol Res. 2015;2015:501361. doi: 10.1155/2015/501361.
    1. Owen JL, Mohamadzadeh M. Microbial activation of gut dendritic cells and the control of mucosal immunity. J Interferon Cytokine Res. 2013;33(11):619–631. doi: 10.1089/jir.2013.0046.
    1. Schlagenhauf U, Jakob L, Eigenthaler M, Segerer S, Jockel-Schneider Y, Rehn M. Regular consumption of Lactobacillus reuteri-containing lozenges reduces pregnancy gingivitis: an RCT. J Clin Periodontol. 2016;43(11):948–954. doi: 10.1111/jcpe.12606.
    1. Schlagenhauf U, Rehder J, Gelbrich G, Jockel-Schneider Y. Consumption of Lactobacillus reuteri-containing lozenges improves periodontal health in navy sailors at sea: a randomized controlled trial. J Periodontol. 2020 doi: 10.1002/jper.19-0393.
    1. Hadj-Hamou R, Senok AC, Athanasiou AE, Kaklamanos EG. Do probiotics promote oral health during orthodontic treatment with fixed appliances? A systematic review. BMC Oral Health. 2020;20(1):126. doi: 10.1186/s12903-020-01109-3.
    1. Gizani S, Petsi G, Twetman S, Caroni C, Makou M, Papagianoulis L. Effect of the probiotic bacterium Lactobacillus reuteri on white spot lesion development in orthodontic patients. Eur J Orthod. 2016;38(1):85–89. doi: 10.1093/ejo/cjv015.
    1. Kohar N, Emmanuel V, Astuti L. Comparison between probiotic lozenges and drinks towards periodontal status improvement of orthodontic patients. Dent J (Majalah Kedokteran Gigi) 2015;48:126. doi: 10.20473/j.djmkg.v48.i3.p126-129.
    1. Benic GZ, Farella M, Morgan XC, Viswam J, Heng NC, Cannon RD, Mei L. Oral probiotics reduce halitosis in patients wearing orthodontic braces: a randomized, triple-blind, placebo-controlled trial. J Breath Res. 2019;13(3):036010. doi: 10.1088/1752-7163/ab1c81.
    1. Habib S. Assessment of the therapeutic potential of a dental probiotic in orthodontic patients affected by gingivitis: a randomized control trial. Master thesis. University of Toronto; 2016.
    1. Seidel CL, Gerlach RG, Wiedemann P, Weider M, Rodrian G, Hader M, Frey B, Gaipl US, Bozec A, Cieplik F, et al. Defining metaniches in the oral cavity according to their microbial composition and cytokine profile. Int J Mol Sci. 2020 doi: 10.3390/ijms21218218.
    1. Berger VW, Ivanova A, Knoll MD. Minimizing predictability while retaining balance through the use of less restrictive randomization procedures. Stat Med. 2003;22(19):3017–3028. doi: 10.1002/sim.1538.
    1. Caton JG, Armitage G, Berglundh T, Chapple ILC, Jepsen S, Kornman KS, Mealey BL, Papapanou PN, Sanz M, Tonetti MS. A new classification scheme for periodontal and peri-implant diseases and conditions - Introduction and key changes from the 1999 classification. J Clin Periodontol. 2018;45(Suppl 20):S1–s8. doi: 10.1111/jcpe.12935.
    1. BMI-for-age (5–19 years). .
    1. Watzl B. Milch und Milchprodukte - "gesund" oder "schädlich"? In: Journalistenseminar der Deutschen Gesellschaft für Ernährung eV - Vegetarisch und Vegan - nur ein Trend? Gästehaus der Universität Hamburg: Prof. Dr. Bernhard Watzl; 2015.
    1. BioGaia - Clinical Studies. .
    1. Skarparis K, Ford C. Venepuncture in adults. Br J Nurs. 2018;27(22):1312–1315. doi: 10.12968/bjon.2018.27.22.1312.
    1. Buowari O. Complications of venepuncture. Adv Biosci Biotechnol. 2013;4:126–128. doi: 10.4236/abb.2013.41A018.
    1. BioGaia Prodentis lozenges: probiotic oral health. .
    1. Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand. 1963;21:533–551. doi: 10.3109/00016356309011240.
    1. Khan S, Cabanilla LL. Periodontal probing depth measurement: a review. Compend Contin Educ Dent. 2009;30(1):12–14, 16, 18–21; quiz 22, 36.
    1. Listgarten MA. Periodontal probing: what does it mean? J Clin Periodontol. 1980;7(3):165–176. doi: 10.1111/j.1600-051x.1980.tb01960.x.
    1. Garnick JJ, Silverstein L. Periodontal probing: probe tip diameter. J Periodontol. 2000;71(1):96–103. doi: 10.1902/jop.2000.71.1.96.
    1. Bulthuis HM, Barendregt DS, Timmerman MF, Loos BG, van der Velden U. Probe penetration in relation to the connective tissue attachment level: influence of tine shape and probing force. J Clin Periodontol. 1998;25(5):417–423. doi: 10.1111/j.1600-051X.1998.tb02465.x.
    1. Attin R. Vorstellung eines neuen Plaqueindex zur Kontrolle und Motivation kieferorthopädischer Patienten. Informationen aus Orthodontie & Kieferorthopädie. 2005;37(04):271–273. doi: 10.1055/s-2005-918210.
    1. Mah J, Prasad N. Dentine phosphoproteins in gingival crevicular fluid during root resorption. Eur J Orthod. 2004;26(1):25–30. doi: 10.1093/ejo/26.1.25.
    1. Twetman S, Derawi B, Keller M, Ekstrand K, Yucel-Lindberg T, Stecksen-Blicks C. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand. 2009;67(1):19–24. doi: 10.1080/00016350802516170.
    1. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–2120. doi: 10.1093/bioinformatics/btu170.
    1. Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. J Res. 2011;17(1):3. doi: 10.14806/ej.17.1.200.
    1. Edgar RC. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26(19):2460–2461. doi: 10.1093/bioinformatics/btq461.
    1. Edgar RC. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10(10):996–998. doi: 10.1038/nmeth.2604.
    1. Lagkouvardos I, Joseph D, Kapfhammer M, Giritli S, Horn M, Haller D, Clavel T. IMNGS: a comprehensive open resource of processed 16S rRNA microbial profiles for ecology and diversity studies. Sci Rep. 2016;6:33721. doi: 10.1038/srep33721.
    1. SILVA database. .
    1. R Core Team. R: a language and environment for statistical computing; R Foundation for Statistical Computing, Vienna, Austria: 2020.
    1. Vegan: community ecology package. .
    1. Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–140. doi: 10.1093/bioinformatics/btp616.
    1. Merle M, Fischbacher D, Liepert A, Grabrucker C, Kroell T, Kremser A, Dreyssig J, Freudenreich M, Schuster F, Borkhardt A, et al. Serum chemokine-release profiles in AML-patients might contribute to predict the clinical course of the disease. Immunol Investig. 2020;49(4):365–385. doi: 10.1080/08820139.2019.1661429.
    1. Merle M, Fischbacher D, Liepert A, Grabrucker C, Kroell T, Kremser A, Dreyssig J, Freudenreich M, Schuster F, Borkhardt A, et al. Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in ‘DC-culture-media’ shifts correlations of released chemokines with antileukemic T-cell reactions. Immunobiology. 2021;226(3):152088. doi: 10.1016/j.imbio.2021.152088.
    1. Fischbacher D, Merle M, Liepert A, Grabrucker C, Kroell T, Kremser A, Dreyßig J, Freudenreich M, Schuster F, Borkhardt A, et al. Cytokine release patterns in mixed lymphocyte culture (MLC) of T-cells with dendritic cells (DC) generated from AML blasts contribute to predict anti-leukaemic t-cell reactions and patients’ response to immunotherapy. Cell Commun Adhes. 2015;22(2–6):49–65. doi: 10.1080/15419061.2016.1223634.
    1. Boeck CL, Amberger DC, Doraneh-Gard F, Sutanto W, Guenther T, Schmohl J, Schuster F, Salih H, Babor F, Borkhardt A, et al. Significance of frequencies, compositions, and/or antileukemic activity of (DC-stimulated) invariant NKT, NK and CIK cells on the outcome of patients with AML, ALL and CLL. J Immunother. 2017;40(6):224–248. doi: 10.1097/cji.0000000000000171.
    1. Dongarra ML, Rizzello V, Muccio L, Fries W, Cascio A, Bonaccorsi I, Ferlazzo G. Mucosal immunology and probiotics. Curr Allergy Asthma Rep. 2013;13(1):19–26. doi: 10.1007/s11882-012-0313-0.
    1. Klauer LK, Ugur S, Doraneh-Gard F, Rogers N, Weinmann M, Krämer D, Rank A, Schmid C, Eiz-Vesper B, Schmetzer HM. IFNy secretion of adaptive and innate immune cells as a parameter to display leukaemia derived dendritic cell (DC leu) mediated immune responses in AML. J Immunother Cancer. 2020;8:5. doi: 10.1136/jitc-2020-ITOC7.23.
    1. Pepeldjiyska E LL, Gao J, Seidel CL, Blasi C, Özkaya E, Schmohl J, Kraemer D, Schmid C, Rank A, Schmetzer HM. Leukemia derived dendritic cell (DCleu) mediated immune response goes along with reduced (leukemia-specific) regulatory T-cells. Submitted in revision; 2022.
    1. Schmohl Joerg MS, Guenther T, Pepeldjyika E, Seidel CL, Wishnu S, Friedhelm S, Doris K, Helmut S, Amely H, Johanna T, Christian R, Helga SM. Expression of Surface-associated 82 kDa proMMP-9 in Lymphatic Leukemia Blast Cells Differentially Correlates With Prognosis. Anticancer Res. 2021;41(8):3891–3898. doi: 10.21873/anticanres.15184.
    1. Vivekananda MR, Vandana KL, Bhat KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management of periodontal disease: a preliminary randomized clinical trial. J Oral Microbiol. 2010;2:5. doi: 10.3402/jom.v2i0.5344.
    1. Tekce M, Ince G, Gursoy H, Dirikan Ipci S, Cakar G, Kadir T, Yilmaz S. Clinical and microbiological effects of probiotic lozenges in the treatment of chronic periodontitis: a 1-year follow-up study. J Clin Periodontol. 2015;42(4):363–372. doi: 10.1111/jcpe.12387.
    1. Iniesta M, Herrera D, Montero E, Zurbriggen M, Matos AR, Marín MJ, Sánchez-Beltrán MC, Llama-Palacio A, Sanz M. Probiotic effects of orally administered Lactobacillus reuteri-containing tablets on the subgingival and salivary microbiota in patients with gingivitis. A randomized clinical trial. J Clin Periodontol. 2012;39(8):736–744. doi: 10.1111/j.1600-051X.2012.01914.x.
    1. Blair RC, Higgins JJ. A comparison of the power of wilcoxon's rank-sum statistic to that of student'st statistic under various nonnormal distributions. J Educ Stat. 1980;5(4):309–335. doi: 10.3102/10769986005004309.
    1. Team R A language and environment for statistical computing. Computing. 2006 doi: 10.1890/0012-9658(2002)083[3097:CFHIWS];2.
    1. Uschner D, Schindler D, Hilgers R-D, Heussen N. randomizeR : an R package for the assessment and implementation of randomization in clinical trials. J Stat Softw. 2018 doi: 10.18637/jss.v085.i08.
    1. Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586. doi: 10.1136/bmj.e7586.
    1. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–207. doi: 10.7326/0003-4819-158-3-201302050-00583.
    1. Musa Trolic I, Todoric Z, Pop Acev D, Makreski P, Pejova B, Spalj S. Effects of the presence of probiotic bacteria in the aging medium on the surface roughness and chemical composition of two dental alloys. Microsc Res Tech. 2019;82(9):1384–1391. doi: 10.1002/jemt.23290.
    1. Trolić IM, Turco G, Contardo L, Serdarević NL, Otmačić H, Ćurković R, Špalj S. Corrosion of nickel-titanium orthodontic archwires in saliva and oral probiotic supplements. Acta Stomatol Croat. 2017;51(4):316–325. doi: 10.15644/asc51/4/6.
    1. Pavlic A, Perissinotto F, Turco G, Contardo L, Spalj S. Do chlorhexidine and probiotics solutions provoke corrosion of orthodontic mini-implants? An in vitro study. Int J Oral Maxillofac Implants. 2019;33(6):1379–1388. doi: 10.11607/jomi.7392.
    1. Sprint (R) II Produktkatalog. .
    1. Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: case definition and diagnostic considerations. J Clin Periodontol. 2018;45(Suppl 20):S44–s67. doi: 10.1111/jcpe.12939.
    1. Brecx MC, Schlegel K, Gehr P, Lang NP. Comparison between histological and clinical parameters during human experimental gingivitis. J Periodontal Res. 1987;22(1):50–57. doi: 10.1111/j.1600-0765.1987.tb01539.x.
    1. Newbrun E. Indices to measure gingival bleeding. J Periodontol. 1996;67(6):555–561. doi: 10.1902/jop.1996.67.6.555.
    1. Tobias G, Spanier AB. Modified gingival index (MGI) classification using dental selfies. Appl Sci. 2020;10(24):8923. doi: 10.3390/app10248923.
    1. Smith RN, Brook AH, Elcock C. The quantification of dental plaque using an image analysis system: reliability and validation. J Clin Periodontol. 2001;28(12):1158–1162. doi: 10.1034/j.1600-051x.2001.281211.x.
    1. Le Fouler A, Jeanne S, Sorel O, Brézulier D. How effective are three methods of teaching oral hygiene for adolescents undergoing orthodontic treatment? The MAHO protocol: an RCT comparing visual, auditory and kinesthetic methods. Trials. 2021;22(1):144. doi: 10.1186/s13063-021-05093-z.
    1. Socransky SS, Haffajee AD, Cugini MA, Smith C, Kent RL., Jr Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134–144. doi: 10.1111/j.1600-051x.1998.tb02419.x.
    1. Kobayashi R, Kobayashi T, Sakai F, Hosoya T, Yamamoto M, Kurita-Ochiai T. Oral administration of Lactobacillus gasseri SBT2055 is effective in preventing Porphyromonas gingivalis-accelerated periodontal disease. Sci Rep. 2017;7(1):545. doi: 10.1038/s41598-017-00623-9.
    1. Romani Vestman N, Chen T, Lif Holgerson P, Ohman C, Johansson I. Oral microbiota shift after 12-week supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289; a randomized control trial. PLoS ONE. 2015;10(5):e0125812. doi: 10.1371/journal.pone.0125812.
    1. Nissen L, Sgorbati B, Biavati B, Belibasakis GN. Lactobacillus salivarius and L. gasseri down-regulate Aggregatibacter actinomycetemcomitans exotoxins expression. Ann Microbiol. 2014;64(2):611–617. doi: 10.1007/s13213-013-0694-x.
    1. Griffen AL, Beall CJ, Campbell JH, Firestone ND, Kumar PS, Yang ZK, Podar M, Leys EJ. Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing. ISME J. 2012;6(6):1176–1185. doi: 10.1038/ismej.2011.191.
    1. Ge X, Rodriguez R, Trinh M, Gunsolley J, Xu P. Oral microbiome of deep and shallow dental pockets in chronic periodontitis. PLoS ONE. 2013;8(6):e65520. doi: 10.1371/journal.pone.0065520.
    1. Costalonga M, Herzberg MC. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett. 2014;162(2 Pt A):22–38. doi: 10.1016/j.imlet.2014.08.017.
    1. Kirakodu S, Chen J, Gonzalez Martinez J, Gonzalez OA, Ebersole J. Microbiome profiles of ligature-induced periodontitis in nonhuman primates across the life span. Infect Immun. 2019 doi: 10.1128/iai.00067-19.
    1. Albandar JM. Global risk factors and risk indicators for periodontal diseases. Periodontol. 2000;2002(29):177–206. doi: 10.1034/j.1600-0757.2002.290109.x.
    1. Kumar PS. Sex and the subgingival microbiome: do female sex steroids affect periodontal bacteria? Periodontol. 2013;61(1):103–124. doi: 10.1111/j.1600-0757.2011.00398.x.
    1. Umeda M, Chen C, Bakker I, Contreras A, Morrison JL, Slots J. Risk indicators for harboring periodontal pathogens. J Periodontol. 1998;69(10):1111–1118. doi: 10.1902/jop.1998.69.10.1111.
    1. Ericsson I, Lindhe J. Effect of longstanding jiggling on experimental marginal periodontitis in the beagle dog. J Clin Periodontol. 1982;9(6):497–503. doi: 10.1111/j.1600-051X.1982.tb02111.x.
    1. Lindhe J, Ericsson I. Effect of ligature placement and dental plaque on periodontal tissue breakdown in the dog. J Periodontol. 1978;49(7):343–350. doi: 10.1902/jop.1978.49.7.343.
    1. Allaker RP, Stephen AS. Use of probiotics and oral health. Curr Oral Health Rep. 2017;4(4):309–318. doi: 10.1007/s40496-017-0159-6.
    1. Meurman JH. Probiotics: do they have a role in oral medicine and dentistry? Eur J Oral Sci. 2005;113(3):188–196. doi: 10.1111/j.1600-0722.2005.00191.x.
    1. Rath-Deschner B, Nogueira AVB, Beisel-Memmert S, Nokhbehsaim M, Eick S, Cirelli JA, Deschner J, Jäger A, Damanaki A. Interaction of periodontitis and orthodontic tooth movement-an in vitro and in vivo study. Clin Oral Investig. 2021 doi: 10.1007/s00784-021-03988-4.
    1. Szkaradkiewicz AK, Stopa J, Karpinski TM. Effect of oral administration involving a probiotic strain of Lactobacillus reuteri on pro-inflammatory cytokine response in patients with chronic periodontitis. Arch Immunol Ther Exp. 2014;62(6):495–500. doi: 10.1007/s00005-014-0277-y.
    1. Wohlfeil M, Scharf S, Siegelin Y, Schacher B, Oremek GM, Sauer-Eppel H, Schubert R, Eickholz P. Increased systemic elastase and C-reactive protein in aggressive periodontitis (CLOI-D-00160R2) Clin Oral Invest. 2012;16(4):1199–1207. doi: 10.1007/s00784-011-0627-7.
    1. Afar B, Engel D, Clark EA. Activated lymphocyte subsets in adult periodontitis. J Periodontal Res. 1992;27(2):126–133. doi: 10.1111/j.1600-0765.1992.tb01814.x.
    1. Sabarish R, Rao SR, Lavu V. Natural T regulatory cells (n Treg) in the peripheral blood of healthy subjects and subjects with chronic periodontitis—a pilot study. J Clin Diagn Res. 2016;10(3):ZC36–ZC39. doi: 10.7860/JCDR/2016/15449.7446.
    1. Cifcibasi E, Ciblak M, Kiran B, Badur S, Firatli E, Issever H, Cintan S. The role of activated cytotoxic T cells in etiopathogenesis of periodontal disease: does it harm or does it heal? Sci Rep. 2015;5:9262. doi: 10.1038/srep09262.
    1. Chen XT, Chen LL, Tan JY, Shi DH, Ke T, Lei LH. Th17 and Th1 lymphocytes are correlated with chronic periodontitis. Immunol Investig. 2016;45(3):243–254. doi: 10.3109/08820139.2016.1138967.
    1. Celenligil H, Kansu E, Eratalay K. Juvenile and rapidly progressive periodontitis. Peripheral blood lymphocyte subpopulations. J Clin Periodontol. 1990;17(4):207–210. doi: 10.1111/j.1600-051X.1990.tb00014.x.
    1. Carrion J, Scisci E, Miles B, Sabino GJ, Zeituni AE, Gu Y, Bear A, Genco CA, Brown DL, Cutler CW. Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential. J Immunol. 2012;189(6):3178–3187. doi: 10.4049/jimmunol.1201053.
    1. Wohlfeil M, Wehner J, Schacher B, Oremek GM, Sauer-Eppel H, Eickholz P. Degree of gingivitis correlates to systemic inflammation parameters. Clin Chim Acta. 2009;401(1–2):105–109. doi: 10.1016/j.cca.2008.11.017.
    1. Kovac V, Poljsak B, Perinetti G, Primozic J. Systemic level of oxidative stress during orthodontic treatment with fixed appliances. Biomed Res Int. 2019;2019:5063565. doi: 10.1155/2019/5063565.
    1. Pahumunto N, Basic A, Östberg AK, Teanpaisan R, Dahlen G. Oral Lactobacillus strains reduce cytotoxicity and cytokine release from peripheral blood mononuclear cells exposed to Aggregatibacter actinomycetemcomitans subtypes in vitro. BMC Microbiol. 2020;20(1):279. doi: 10.1186/s12866-020-01959-5.
    1. Bene KP, Kavanaugh DW, Leclaire C, Gunning AP, MacKenzie DA, Wittmann A, Young ID, Kawasaki N, Rajnavolgyi E, Juge N. Lactobacillus reuteri surface mucus adhesins upregulate inflammatory responses through interactions with innate C-type lectin receptors. Front Microbiol. 2017;8:321. doi: 10.3389/fmicb.2017.00321.
    1. Rizzello V, Bonaccorsi I, Dongarra ML, Fink LN, Ferlazzo G. Role of natural killer and dendritic cell crosstalk in immunomodulation by commensal bacteria probiotics. J Biomed Biotechnol. 2011;2011:473097. doi: 10.1155/2011/473097.
    1. Bui VT, Tseng HC, Kozlowska A, Maung PO, Kaur K, Topchyan P, Jewett A. Augmented IFN-gamma and TNF-alpha induced by probiotic bacteria in NK cells mediate differentiation of stem-like tumors leading to inhibition of tumor growth and reduction in inflammatory cytokine release; regulation by IL-10. Front Immunol. 2015;6:576. doi: 10.3389/fimmu.2015.00576.
    1. Ciprandi G. Vitamin D3 plus Lactobacillus reuteri DSM 17938 as adjuvant for allergen immunotherapy: a preliminary experience. Jacobs J Allergy Immunol. 2000;2(2):014.
    1. Ivory K, Wilson AM, Sankaran P, Westwood M, McCarville J, Brockwell C, Clark A, Dainty JR, Zuidmeer-Jongejan L, Nicoletti C. Oral delivery of a probiotic induced changes at the nasal mucosa of seasonal allergic rhinitis subjects after local allergen challenge: a randomised clinical trial. PLoS ONE. 2013;8(11):e78650. doi: 10.1371/journal.pone.0078650.

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