Abstract
Introduction
Multiple sclerosis (MS) is a chronic inflammatory demyelinating autoimmune disease that affects the central nervous system. Since immune system plays a key role in this disease, patients with MS can present higher risk of infections.
Purpose
This study aimed to investigate the prevalence of Candida spp. in the oral cavity of MS patients in relation to a control group
Methods
In total, 100 individuals were selected: 55 diagnosed with MS and 45 healthy individuals (control group). Saliva samples were collected and seeded in culture media selecting for Candida. Following an incubation period of 48 h, colony-forming units (CFU mL−1) were counted and colonies were isolated for Candida species identification by multiplex PCR. The results were analysed by chi-squared and Mann–Whitney U statistical tests considering a significance level of 5%.
Results
Candida spp. were confirmed in the oral cavity of 50.09% patients in the MS group and 35.55% individuals in the control group. In individuals positive for the growth of Candida spp., the median values of Candida colonies were 220 CFU mL−1 for the MS group and 120 CFU mL−1 for the control group. However, no statistically significant differences were observed between groups for both prevalence and CFU mL−1 count. Of the Candida species identified, 73.91% were C. albicans, 21.73% C. glabrata, 2.17% C. tropicalis, and 2.17% C. krusei.
Conclusions
The colonization of Candida spp. in the oral cavity of individuals with multiple sclerosis was higher than in the control group; however these findings were not proven to be statistically significant.
Similar content being viewed by others
References
Milo R, Miller A. Revised diagnostic criteria of multiple sclerosis. Autoimmun Rev. 2014;13(4–5):518–24. https://doi.org/10.1016/j.autrev.2014.01.012.
Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 2014;48–49:134–42. https://doi.org/10.1016/j.jaut.2014.01.022.
Kingwell E, Marriott JJ, Jette N, Pringsheim T, Makhani N, Morrow SA, et al. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol. 2013;13:128. https://doi.org/10.1186/1471-2377-13-128.
Steinman L. Immunology of relapse and remission in multiple sclerosis. Annu Rev Immunol. 2014;32:257–81. https://doi.org/10.1146/annurev-immunol-032713-120227.
Huang WJ, Chen WW, Zhang X. Multiple sclerosis: pathology, diagnosis and treatments. Exp Ther Med. 2017;13(6):3163–6. https://doi.org/10.3892/etm.2017.4410.
Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. 2018;378(2):169–80. https://doi.org/10.1056/NEJMra1401483.
Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–86. https://doi.org/10.1212/WNL.0000000000000560.
Kanchandani R, Howe JG. Lhermitte's sign in multiple sclerosis: a clinical survey and review of the literature. J Neurol Neurosurg Psychiatry. 1982;45(4):308–12. https://doi.org/10.1136/jnnp.45.4.308.
Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–17. https://doi.org/10.1016/S0140-6736(08)61620-7.
Amato MP, Derfuss T, Hemmer B, Liblau R, Montalban X, Soelberg Sorensen P, et al. Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop. Mult Scler. 2018;24(5):590–603. https://doi.org/10.1177/1352458516686847.
McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8(9):913–9. https://doi.org/10.1038/ni1507.
Hemmer B, Kerschensteiner M, Korn T. Role of the innate and adaptive immune responses in the course of multiple sclerosis. Lancet Neurol. 2015;14(4):406–19. https://doi.org/10.1016/S1474-4422(14)70305-9.
Luna G, Alping P, Burman J, Fink K, Fogdell-Hahn A, Gunnarsson M, et al. Infection risks among patients with multiple sclerosis treated with Fingolimod, Natalizumab, Rituximab, and Injectable Therapies. JAMA Neurol. 2019. https://doi.org/10.1001/jamaneurol.2019.3365.
Allizond V, Scutera S, Rossi S, Musso T, Crocilla C, Cavalla P, et al. Polymorphonuclear cell functional impairment in relapsing remitting multiple sclerosis patients: preliminary data. PLoS ONE. 2015;10(6):e0131557. https://doi.org/10.1371/journal.pone.0131557.
de Barros PP, Rossoni RD, de Souza CM, Scorzoni L, Fenley JC, Junqueira JC. Candida biofilms: an update on developmental mechanisms and therapeutic challenges. Mycopathologia. 2020;185(3):415–24. https://doi.org/10.1007/s11046-020-00445-w.
Junqueira JC, Vilela SF, Rossoni RD, Barbosa JO, Costa AC, Rasteiro VM, et al. Oral colonization by yeasts in HIV-positive patients in Brazil. Rev Inst Med Trop Sao Paulo. 2012;54(1):17–24. https://doi.org/10.1590/s0036-46652012000100004.
de Barros PP, Rossoni RD, De Camargo RF, Junqueira JC, Jorge AO. Temporal profile of biofilm formation, gene expression and virulence analysis in Candida albicans Strains. Mycopathologia. 2017;182(3–4):285–95. https://doi.org/10.1007/s11046-016-0088-2.
Chouhan S, Kallianpur S, Prabhu KT, Tijare M, Kasetty S, Gupta S. Candidal prevalence in diabetics and its species identification. Int J Appl Basic Med Res. 2019;9(1):49–544. https://doi.org/10.4103/ijabmr.IJABMR_259_18.
Chen YC, Eisner JD, Kattar MM, Rassoulian-Barrett SL, LaFe K, Yarfitz SL, et al. Identification of medically important yeasts using PCR-based detection of DNA sequence polymorphisms in the internal transcribed spacer 2 region of the rRNA genes. J Clin Microbiol. 2000;38(6):2302–10.
Vasconcelos CC, Thuler LC, Rodrigues BC, Calmon AB, Alvarenga RM. Multiple sclerosis in Brazil: a systematic review. Clin Neurol Neurosurg. 2016;151:24–30. https://doi.org/10.1016/j.clineuro.2016.07.011.
Kraft-Bodi E, Jorgensen MR, Keller MK, Kragelund C, Twetman S. Effect of probiotic bacteria on oral Candida in Frail Elderly. J Dent Res. 2015;94(9 Suppl):181S–S186186. https://doi.org/10.1177/0022034515595950.
Marques VD, Passos GRD, Mendes MF, Callegaro D, Lana-Peixoto MA, Comini-Frota ER, et al. Brazilian consensus for the treatment of multiple sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis. Arq Neuropsiquiatr. 2018;76(8):539–54. https://doi.org/10.1590/0004-282X20180078.
Plosker GL. Interferon-beta-1b: a review of its use in multiple sclerosis. CNS Drugs. 2011;25(1):67–88. https://doi.org/10.2165/11206430-000000000-00000.
Mehling M, Kappos L, Derfuss T. Fingolimod for multiple sclerosis: mechanism of action, clinical outcomes, and future directions. Curr Neurol Neurosci Rep. 2011;11(5):492–7. https://doi.org/10.1007/s11910-011-0216-9.
Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006;354(9):899–910. https://doi.org/10.1056/NEJMoa044397.
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, et al. Alemtuzumab more effective than interferon beta-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012;78(14):1069–78. https://doi.org/10.1212/WNL.0b013e31824e8ee7.
Voge NV, Alvarez E. Monoclonal antibodies in multiple sclerosis: present and future. Biomedicines. 2019. https://doi.org/10.3390/biomedicines7010020.
Alrayyes SF, Alruwaili HM, Taher IA, Elrahawy KM, Almaeen AH, Ashekhi AO, et al. Oral Candidal carriage and associated risk indicators among adults in Sakaka, Saudi Arabia. BMC Oral Health. 2019;19(1):86. https://doi.org/10.1186/s12903-019-0775-8.
Aminzadeh A, Sabeti Sanat A, Nik AS. Frequency of candidiasis and colonization of Candida albicans in relation to oral contraceptive pills. Iran Red Crescent Med J. 2016;18(10):e38909. https://doi.org/10.5812/ircmj.38909.
Lll KG, Klimczak A, Rachubinski P, Jaglowska A, Kwapiszewska A. Consumption of sweetened beverages as a risk factor of colonization of oral cavity by fungi—eating habits of university students. Ann Parasitol. 2015;61(3):175–82. https://doi.org/10.17420/ap6103.04.
Mousa MA, Lynch E, Kielbassa AM. Denture-related stomatitis in new complete denture wearers and its association with Candida species colonization: a prospective case-series. Quintessence Int. 2020;51(7):554–65. https://doi.org/10.3290/j.qi.a44630.
Khadija B, Abbasi A, Khan S, Nadeem M, Badshah L, Faryal R. Isolation of pathogenic Candida species from oral cavity of postpartum females, and its association with obstetric and dental problems. Microb Pathog. 2019;131:40–6. https://doi.org/10.1016/j.micpath.2019.03.022.
Menezes TO, Rodrigues MC, Nogueira BM, Menezes SA, Silva SH, Vallinoto AC. Oral and systemic manifestations in HIV-1 patients. Rev Soc Bras Med Trop. 2015;48(1):83–6. https://doi.org/10.1590/0037-8682-0179-2014.
Pisa D, Alonso R, Carrasco L. Fungal infection in a patient with multiple sclerosis. Eur J Clin Microbiol Infect Dis. 2011;30(10):1173–80. https://doi.org/10.1007/s10096-011-1206-1.
Benito-Leon J, Pisa D, Alonso R, Calleja P, Diaz-Sanchez M, Carrasco L. Association between multiple sclerosis and Candida species: evidence from a case-control study. Eur J Clin Microbiol Infect Dis. 2010;29(9):1139–45. https://doi.org/10.1007/s10096-010-0979-y.
Purzycki CB, Shain DH. Fungal toxins and multiple sclerosis: a compelling connection. Brain Res Bull. 2010;82(1–2):4–6. https://doi.org/10.1016/j.brainresbull.2010.02.012.
Fraga-Silva TF, Mimura LA, Marchetti CM, Chiuso-Minicucci F, Franca TG, Zorzella-Pezavento SF, et al. Experimental autoimmune encephalomyelitis development is aggravated by Candida albicans infection. J Immunol Res. 2015;2015:635052. https://doi.org/10.1155/2015/635052.
Acknowledgements
We thank the National Council for Scientific and Technological Development (CNPq), Grant: 306330/2018-0, for the support.
Funding
No funding was received.
Author information
Authors and Affiliations
Contributions
The experiments are performed by ETSC, LMAFG, DHS, RPCDC, GSO, PPB, KN, CPT, JCJ. The experiments are conceived and designed by ETSC, JCJ. The data are analyzed by ETSC, LMAFG, JCJ. The paper is written by ETSC, LMAFG, PPB, JCJ. Supervision is done by JCJ.
Corresponding author
Ethics declarations
Conflict of interest
Lívia Mara Alves Figueiredo-Godoi, Patrícia Pimentel de Barros, Juliana Campos Junqueira declare that they have no conflict of interest. Eliana Tomomi Shimabukuro da Cunha, Diogo Haddad Santos, Rafael Paterno Castello Dias Carneiro, Guilherme Sciascia do Olival, Keila Narimatsu, Charles Peter Tilbery have received personal fees from Biogen-Idec, personal fees from Merck-Serono, personal fees from TEVA, personal fees from Genzyme and personal fees from Roche, outside the submitted work.
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Research Ethics Committee Involving Human Beings of the Institute of Science and Technology of UNESP—CAAE: 06066818.3.0000.0077) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Handling Editor: Marcia de Souza Carvalho Melhem.
Rights and permissions
About this article
Cite this article
da Cunha, E.T.S., Figueiredo-Godoi, L.M.A., Santos, D.H. et al. Oral Colonization by Candida Species in Patients with Multiple Sclerosis. Mycopathologia 185, 983–991 (2020). https://doi.org/10.1007/s11046-020-00486-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11046-020-00486-1