Top

BMC Oral Health

Published in:

Open Access 01-12-2023 | Probiotics | Research

Effect of lactobacillus reuteri-derived probiotic nano-formulation on recurrent aphthous stomatitis: a double-blinded randomized clinical trial

Authors: Nazafarin Samiraninezhad, Hojat Kazemi, Mostafa Rezaee, Ahmad Gholami

Published in: BMC Oral Health | Issue 1/2023

Abstract

Objectives

We aimed to assess the therapeutic effects of a topical probiotic nano-formulation derived from Lactobacillus reuteri on treating recurrent aphthous stomatitis.

Materials and methods

60 participants were randomly allocated into two groups (control and probiotic). Probiotic group administered topical probiotic nano-formulation three times a day for seven days. The control group administered a standard analgesic oral rinse. The size of ulcer(s) and pain severity were recorded on days 0, 3, 5, and 7 after intervention.

Results

Before the intervention, the groups had no significant differences in terms of pain severity (P-value = 0.28) and lesion size (P-value = 0.24). Both groups exhibited significant reductions in pain severity and lesion size over the course of the intervention. After one week, the probiotic group had a notably larger lesion size reduction than the control group (P-value = 0.01). The probiotic group also showed a significantly greater reduction in pain severity than the control group (P-value = 0.04).

Conclusions

Applying topical probiotic nano-formulation derived from Lactobacillus reuteri three times a day decreased lesion size and pain severity in RAS patients faster than the local analgesic oral rinse.

Clinical relevance

Lactobacillus reuteri-derived probiotic nano-formulation might be a promising treatment option for RAS.

Edgar NR, Saleh D, Miller RA. Recurrent aphthous stomatitis: a review. J Clin Aesthetic Dermatol. 2017;10(3):26.

Raj K, Vadivel JK, Sivaswamy V. Prevalence and age related risk of three clinical variants of Aphthous Stomatitis: a retrospective study. Indian J Forensic Med Toxicol. 2020;14(4):5643–9.

Jahromi NZ, Ghapanchi J, Pourshahidi S, Zahed M, Ebrahimi H. Clinical evaluation of high and low-level laser treatment (CO2vsInGaAlp diode laser) for recurrent aphthous stomatitis. J Dent. 2017;18(1):17.

Banu S, Ramakrishnan M. A comprehensive review on oral aphthous Ulcer. Indian J Public Health Res Dev, vol. 10, no. 11, 2019.

Cui RZ, Bruce AJ, Rogers RS. Recurrent aphthous stomatitis. Clin Dermatol. 2016;34(4):475–81.CrossRefPubMed

Gallo Cde B, Mimura MA, Sugaya NN. Psychological stress and recurrent aphthous stomatitis, (in eng), Clinics (Sao Paulo, Brazil), vol. 64, no. 7, pp. 645-8, 2009, https://doi.org/10.1590/s1807-59322009000700007.

Eversole LR. Immunopathology of oral mucosal ulcerative, desquamative, and bullous diseases. Selective review of the literature, (in eng), Oral surgery, oral medicine, and oral pathology, vol. 77, no. 6, pp. 555 – 71, Jun 1994, https://doi.org/10.1016/0030-4220(94)90312-3.

Hunter IP, Ferguson MM, Scully C, Galloway AR, Main AN, Russell RI. Effects of dietary gluten elimination in patients with recurrent minor aphthous stomatitis and no detectable gluten enteropathy, (in eng), Oral surgery, oral medicine, and oral pathology, vol. 75, no. 5, pp. 595-8, May 1993, https://doi.org/10.1016/0030-4220(93)90232-s.

Natah SS, Konttinen YT, Enattah NS, Ashammakhi N, Sharkey KA, Häyrinen-Immonen R. Recurrent aphthous ulcers today: a review of the growing knowledge, (in eng), International journal of oral and maxillofacial surgery, vol. 33, no. 3, pp. 221 – 34, Apr 2004, https://doi.org/10.1006/ijom.2002.0446.

10.

McBride DR. Management of aphthous ulcers, (in eng), American family physician, vol. 62, no. 1, pp. 149 – 54, 160, Jul 1 2000.

11.

Altenburg A, Zouboulis CC. Current concepts in the treatment of recurrent aphthous stomatitis, (in eng), Skin therapy letter, vol. 13, no. 7, pp. 1–4, Sep 2008.

12.

Scully C, Gorsky M, Lozada-Nur F. The diagnosis and management of recurrent aphthous stomatitis: a consensus approach, (in eng), Journal of the American Dental Association (1939), vol. 134, no. 2, pp. 200-7, Feb 2003, https://doi.org/10.14219/jada.archive.2003.0134.

13.

Belenguer-Guallar I, Jiménez-Soriano Y, Claramunt-Lozano A. Treatment of recurrent aphthous stomatitis. A literature review. (in eng) Journal of Clinical and Experimental Dentistry. Apr 2014;6(2):e168–74. https://doi.org/10.4317/jced.51401.

14.

Eisen D, Lynch DP. Selecting topical and systemic agents for recurrent aphthous stomatitis, (in eng), Cutis, vol. 68, no. 3, pp. 201-6, Sep 2001.

15.

Choi E, Nahm FS, Han WK, Lee PB, Jo J. Topical agents: a thoughtful choice for multimodal analgesia, (in eng). Korean J Anesthesiol. Oct 2020;73(5):384–93. https://doi.org/10.4097/kja.20357.

16.

Karavana SY et al. A new approach to the treatment of recurrent aphthous stomatitis with bioadhesive gels containing cyclosporine A solid lipid nanoparticles: in vivo/in vitro examinations, (in eng), Int J Nanomedicine, vol. 7, pp. 5693 – 704, 2012, https://doi.org/10.2147/ijn.S36883.

17.

Bakhshi M, Mahboubi A, Jaafari MR, Ebrahimi F, Tofangchiha M, Alizadeh A, COMPARATIVE EFFICACY OF 1% CURCUMIN NANOMICELLE GEL AND 2% CURCUMIN GEL FOR TREATMENT OF RECURRENT APHTHOUS STOMATITIS. A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL, (in eng). J Evid Based Dent Pract. Jun 2022;22(2):101708. https://doi.org/10.1016/j.jebdp.2022.101708.

18.

Sadeghian R, Rohani B, Golestannejad Z, Sadeghian S, Mirzaee S. Comparison of therapeutic effect of mucoadhesive nano-triamcinolone gel and conventional triamcinolone gel on oral lichen planus. Dent Res J. 2019;16(5):277.CrossRef

19.

Scribante A, Butera A, Alovisi M. Customized minimally invasive protocols for the clinical and microbiological management of the oral microbiota. Volume 10. ed: MDPI; 2022. p. 675.

20.

Caufield PW, Li Y, Dasanayake A, Saxena D. Diversity of lactobacilli in the oral cavities of young women with dental caries, (in eng), Caries research, vol. 41, no. 1, pp. 2–8, 2007, https://doi.org/10.1159/000096099.

21.

Busscher HJ, Mulder AF, van der Mei HC. In vitro adhesion to enamel and in vivo colonization of tooth surfaces by Lactobacilli from a bio-yoghurt, (in eng), Caries research, vol. 33, no. 5, pp. 403-4, Sep-Oct 1999, https://doi.org/10.1159/000016541.

22.

Lima LM, Motisuki C, Spolidorio DM, Santos-Pinto L. In vitro evaluation of probiotics microorganisms adhesion to an artificial caries model, (in eng), European journal of clinical nutrition, vol. 59, no. 7, pp. 884-6, Jul 2005, https://doi.org/10.1038/sj.ejcn.1602158.

23.

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, (in eng). Acta Odontol Scand. 2009;67(1):19–24. https://doi.org/10.1080/00016350802516170.CrossRefPubMed

24.

Harini PM, Anegundi RT. Efficacy of a probiotic and chlorhexidine mouth rinses: a short-term clinical study, (in eng), Journal of the Indian Society of Pedodontics and Preventive Dentistry, vol. 28, no. 3, pp. 179 – 82, Jul-Sep 2010, https://doi.org/10.4103/0970-4388.73799.

25.

Hasslöf P, Hedberg M, Twetman S, Stecksén-Blicks C. Growth inhibition of oral mutans streptococci and candida by commercial probiotic lactobacilli–an in vitro study, (in eng), BMC oral health, vol. 10, p. 18, Jul 2 2010, https://doi.org/10.1186/1472-6831-10-18.

26.

Michalek SM, Hirasawa M, Kiyono H, Ochiai K, McGhee JR. Oral ecology and virulence of Lactobacillus casei and Streptococcus mutans in gnotobiotic rats, (in eng), Infection and immunity, vol. 33, no. 3, pp. 690-6, Sep 1981, https://doi.org/10.1128/iai.33.3.690-696.1981.

27.

Nirmala M, Smitha SG, Kamath GJ. A study to assess the efficacy of local application of oral probiotic in treating recurrent aphthous Ulcer and oral candidiasis, (in eng). Indian J Otolaryngol head neck Surgery: Official Publication Association Otolaryngologists India. Oct 2019;71:113–7. https://doi.org/10.1007/s12070-017-1139-9.

28.

Pedersen AML, Bukkehave KH, Bennett EP, Twetman S. Effect of Lozenges Containing Lactobacillus reuteri on the Severity of Recurrent Aphthous Ulcers: a Pilot Study, (in eng), Probiotics and antimicrobial proteins, vol. 12, no. 3, pp. 819–823, Sep 2020, https://doi.org/10.1007/s12602-019-09586-x.

29.

Ślebioda Z, Szponar E, Kowalska A. Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review, Archivum immunologiae et therapiae experimentalis, vol. 62, no. 3, pp. 205–215, 2014.

30.

Kim Y-j, Choi YS, Baek KJ, Yoon S-H, Park HK, Choi Y. Mucosal and salivary microbiota associated with recurrent aphthous stomatitis. BMC Microbiol. 2016;16(1):1–10.CrossRef

31.

Kim YJ, Choi YS, Baek KJ, Yoon SH, Park HK, Choi Y. Mucosal and salivary microbiota associated with recurrent aphthous stomatitis, (in eng), BMC microbiology, vol. 16 Suppl 1, p. 57, Apr 1 2016, https://doi.org/10.1186/s12866-016-0673-z.

32.

Cristofori F, Dargenio VN, Dargenio C, Miniello VL, Barone M, Francavilla R. Anti-inflammatory and immunomodulatory effects of probiotics in gut inflammation: a door to the body. Front Immunol. 2021;12:578386.CrossRefPubMedPubMedCentral

33.

Hardy H, Harris J, Lyon E, Beal J, Foey AD. Probiotics, prebiotics and immunomodulation of gut mucosal defences: homeostasis and immunopathology, (in eng), Nutrients, vol. 5, no. 6, pp. 1869 – 912, May 29 2013, https://doi.org/10.3390/nu5061869.

34.

Javanshir N et al. Evaluation of the Function of Probiotics, Emphasizing the Role of their Binding to the Intestinal Epithelium in the Stability and their Effects on the Immune System, (in eng), Biol Proced Online, vol. 23, no. 1, p. 23, Dec 1 2021, https://doi.org/10.1186/s12575-021-00160-w.

35.

Rao RK, Samak G. Protection and Restitution of Gut Barrier by Probiotics: Nutritional and Clinical Implications, (in eng), Curr Nutr Food Sci, vol. 9, no. 2, pp. 99–107, May 1 2013, https://doi.org/10.2174/1573401311309020004.

36.

Lazar V et al. Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer, (in eng), Front Immunol, vol. 9, p. 1830, 2018, https://doi.org/10.3389/fimmu.2018.01830.

37.

Baral KC, Bajracharya R, Lee SH, Han HK. Advancements in the Pharmaceutical Applications of Probiotics: dosage forms and Formulation Technology, (in eng). Int J Nanomedicine. 2021;16:7535–56. https://doi.org/10.2147/ijn.S337427.CrossRefPubMedPubMedCentral

38.

Pedersen AML, Bukkehave KH, Bennett EP, Twetman S. Effect of lozenges containing Lactobacillus reuteri on the severity of recurrent aphthous ulcers: a pilot study. Probiotics and Antimicrobial Proteins, vol. 12, no. 3, pp. 819–23, 2020/09/01 2020, https://doi.org/10.1007/s12602-019-09586-x.

39.

Cheng B, Zeng X, Liu S, Zou J, Wang Y. The efficacy of probiotics in management of recurrent aphthous stomatitis: a systematic review and meta-analysis, Scientific Reports, vol. 10, no. 1, p. 21181, 2020/12/03 2020, https://doi.org/10.1038/s41598-020-78281-7.

40.

Aggour RL, Mahmoud SH, Abdelwhab A. Evaluation of the effect of probiotic lozenges in the treatment of recurrent aphthous stomatitis: a randomized, controlled clinical trial. Clin Oral Invest, vol. 25, no. 4, pp. 2151–8, 2021/04/01 2021, https://doi.org/10.1007/s00784-020-03527-7.

41.

Butera A et al. Paraprobiotics in Non-Surgical Periodontal Therapy: Clinical and Microbiological Aspects in a 6-Month Follow-Up Domiciliary Protocol for Oral Hygiene, (in eng), Microorganisms, vol. 10, no. 2, Feb 1 2022, https://doi.org/10.3390/microorganisms10020337.

Title: Effect of lactobacillus reuteri-derived probiotic nano-formulation on recurrent aphthous stomatitis: a double-blinded randomized clinical trial
Authors: Nazafarin Samiraninezhad
Hojat Kazemi
Mostafa Rezaee
Ahmad Gholami
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Probiotics
Stomatitis Aphthosa
Published in: BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI: https://doi.org/10.1186/s12903-023-03756-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effect of lactobacillus reuteri-derived probiotic nano-formulation on recurrent aphthous stomatitis: a double-blinded randomized clinical trial

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Please log in to get access to this content

Other articles of this Issue 1/2023

Effects of blue-light LED toothbrush on reducing dental plaque and gingival inflammation in orthodontic patients with fixed appliances: a crossover randomized controlled trial

Sella turcica variations in patients with transverse skeletal discrepancies versus patients with normal transverse relationships. a cross- sectional study

Outcomes of endodontic microsurgery using different calcium silicate–based retrograde filling materials: a cohort retrospective cone-beam computed tomographic analysis

Evaluation of recurrence, mortality and treatment complications of oral squamous cell carcinoma in public health centers in Shiraz during 2010 to 2020

Oral health-related quality of life and depressive symptoms in adults: longitudinal associations of the English Longitudinal Study of Ageing (ELSA)

MDP-salts as an adhesion promoter with MDP-primers and self-adhesive resin cement for zirconia cementation