Mecanismos de ação de <i>Lactobacillus</i> spp. no tratamento de candidíase oral

Ferreira, R. L. P. S.; Nova, B. G. V.; Carmo, M. S.; Abreu, A. G.

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Brazilian Journal of Biology

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Original Article • Braz. J. Biol. 84 • 2024 • https://doi.org/10.1590/1519-6984.282609 copiar

Mecanismos de ação de Lactobacillus spp. no tratamento de candidíase oral

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

Candida albicans está frequentemente associada à candidíase oral e os perfis de resistência aos medicamentos têm contribuído para o aumento da morbidade e mortalidade. Sabe-se que Lactobacillus spp. atuam competindo pela adesão ao epitélio, absorção de nutrientes e modulam a microbiota humana. Portanto, são importantes para auxiliar no equilíbrio microbiológico do hospedeiro e reduzir o crescimento de Candida spp. Até o momento não há relatos na literatura de revisões correlacionando o uso de Lactobacillus spp. no tratamento da candidíase oral. Assim, esta revisão tem como objetivo destacar os mecanismos de ação de Lactobacillus spp. e métodos que podem ser utilizados no tratamento da candidíase oral. Trata-se de um estudo realizado a partir da busca em bases como: PubMed Central e Scientific Electronic Library Online, utilizando as seguintes palavras-chave: “Oral Candidiasis” e “Lactobacillus”. Foram incluídos artigos originais sobre candidíase oral, com análises in vitro e in vivo, publicados de 2012 a 2022. Lactobacillus rhamnosus foi o microrganismo mais utilizado nos experimentos contra Candida, atuando principalmente na redução de biofilme, filamentação e competindo por sítios de adesão de Candida spp. Entre os estudos in vivo, a maioria dos pesquisadores utilizou modelos de camundongos imunossuprimidos para infecção por Candida. Os estudos mostraram que os Lactobacillus possuem grande potencial como probiótico, atuando principalmente na prevenção e tratamento de doenças da mucosa. Assim, o uso de Lactobacillus pode ser uma boa estratégia para o tratamento da candidíase oral.

Palavras-chave:
candidíase oral; probióticos; Lactobacillus; Candida

Lactobacillus species	Concentration	Candida species	Concentration	Main Assays	Main Effects	References
L. acidophilus,	10² to 10¹⁰ CFU/mL	C. albicans,	1.5×10³ to 10⁶ CFU/mL	Co-aggregation;	Both L. acidophilus and L. plantarum inhibited the growth of most of the oral Candida species, isolated from HIV/AIDS patients.	Salari and Almani (2020)SALARI, S. and ALMANI, P.G.N., 2020. Antifungal effects of Lactobacillus acidophilus and Lactobacillus plantarum against different oral Candida species isolated from HIV/AIDS patients: an in vitro study. Journal of Oral Microbiology, vol. 12, no. 1, pp. 1769386. http://doi.org/10.1080/20002297.2020.1769386. PMid:32922676. http://doi.org/10.1080/20002297.2020.176...
L. plantarum		C. parapsilosis,		Agar overlay interference;
		C. glabrata,		MIC.
		C. kefyr and
		C. krusei
L. paracasei 28.4	10⁶ to 10⁹ cells/mL	C. albicans (ATCC 18804),	10⁶ to 10⁷ cells/mL	Agar overlay interference;	The probiotic-gellan gum formulations provide a released of L. paracasei cells of 24 h; showed inhibitory, anti-biofilm and anti-hyphae activity.	Ribeiro et al. (2020)RIBEIRO, F.C., JUNQUEIRA, J.C., DOS SANTOS, J.D., DE BARROS, P.P., ROSSONI, R.D., SHUKLA, S., FUCHS, B.B., SHUKLA, A. and MYLONAKIS, E., 2020. Development of probiotic formulations for oral candidiasis prevention: gellan gum as a carrier to deliver Lactobacillus paracasei 28.4. Antimicrobial Agents and Chemotherapy, vol. 64, no. 6, e02323-19. http://doi.org/10.1128/AAC.02323-19. PMid:32253208. http://doi.org/10.1128/AAC.02323-19...
		C. albicans 60,		Biofilm;
		C. albicans 14		Effect of formulation on hyphae production.
L. acidophilus (ATCC 4356),	1x10⁷ cells/mL	C. albicans (ATCC 10231)	1x10 ⁶ cells/mL	Disk diffusion susceptibility test;	L. casei and L. rhamnosus GG exhibited stronger antifungal activity against blastoconidia and biofilm of C. albicans, as well as inhibited formation of Candida biofilm on denture surface.	Song and Lee (2017)SONG, Y.G. and LEE, S.H., 2017. Inhibitory effects of Lactobacillus rhamnosus and Lactobacillus casei on Candida biofilm of denture surface. Archives of Oral Biology, vol. 76, pp. 1-6. http://doi.org/10.1016/j.archoralbio.2016.12.014. PMid:28063305. http://doi.org/10.1016/j.archoralbio.201...
L. casei (ATCC 334),				Biofilm;
L. rhamnosus GG (ATCC 53103)				MIC.
L. paracasei (1.1, 3.1, 4.2, 6.2, 7.5, 8.4, 10.5, 11.6, 15.8, 16.4, 17.1, 20.3, 21.4, 23.4, 24.1, 25.4, 26.1, 27.1, 28.4, 37.1, 39.2),	10⁷ cells/mL Supernatant	C. albicans ATCC 18804,	10⁷ cells mL⁻¹	Antibacterial activities in planktonic cultures;	L. rhamnosus 5.2, L. fermentum 20.4 and L. paracasei 28.4 exhibited the most significant inhibitory activity against C. albicans (ATCC 18804). The three strains of lactobacillus down-regulated expression of C. albicans biofilm specific genes (ALS3, HWP1, CPH1 and EFG1)	Rossoni et al. (2018)ROSSONI, R.D., BARROS, P.P., DE ALVARENGA, J.A., RIBEIRO, F.C., VELLOSO, M.D.S., FUCHS, B.B., MYLONAKIS, E., JORGE, A.O.C. and JUNQUEIRA, J.C., 2018. Antifungal activity of clinical Lactobacillus strains against Candida albicans biofilms: identification of potential probiotic candidates to prevent oral candidiasis. Biofouling, vol. 34, no. 2, pp. 212-225. http://doi.org/10.1080/08927014.2018.1425402. PMid:29380647. http://doi.org/10.1080/08927014.2018.142...
L. rhamnosus (5.2, 13.1, 19.3, 19.9, 36.4),		C. albicans CA60 and CA230S		Biofilm;
L. fermentum (14.5, 20.4, 31.4)				C. albicans gene expression by RT-PCR.
L. reuteri (DSM 17938 and ATCC PTA 5289)	10³ to 10⁹ CFU/mL	C. albicans (CBS 562 NT and CCUG 46390),	0.2 at 500 nm	Co-aggregation;	Both L. reuteri strains showed co-aggregation abilities with the yeasts. The lactobacilli almost completely inhibited the growth of C. albicans and C. parapsilosis, but did not affect C. krusei.	Jorgensen et al. (2017)JØRGENSEN, M.R., KRAGELUND, C., JENSEN, P.Ø., KELLER, M.K. and TWETMAN, S., 2017. Probiotic Lactobacillus reuteri has antifungal effects on oral Candida species in vitro. Journal of Oral Microbiology, vol. 9, no. 1, pp. 1274582. http://doi.org/10.1080/20002297.2016.1274582. PMid:28326154. http://doi.org/10.1080/20002297.2016.127...
	supernatant	C. dubliniensis (41_3 ZZMK and CCUG 48722),		Agar overlay interference test;	The pH measurements suggested that C. krusei can resist the acids produced by the lactobacilli.
		C. glabrata (CBS 863 and		pH effect;
		CCUG 63819),		H₂O₂ production by the lactobacilli.
		C. krusei (RV 491 and CCUG 56126),
		C. parapsilosis (26 PBS and CCUG 56136),
		C. tropicalis (DSM 7524 and CCUG 47037).
L. rhamnosus GG	OD₆₀₀ of 0.669	C. albicans (SC 5314)	5x10⁶ /mL	Cell culture and generation of three-dimensional mucosal models; Infection of RHOEs and TR146 cell monolayers; Epithelial cell damage; ELISA, Adhesion and Invasion assays; Quantification of RNA-Seq; DNA sequencing.	L. rhamnosus protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage in model of oral candidiasis.	Mailander-Sánchez et al. (2017)MAILÄNDER-SÁNCHEZ, D., BRAUNSDORF, C., GRUMAZ, C., MÜLLER, C., LORENZ, S., STEVENS, P., WAGENER, J., HEBECKER, B., HUBE, B., BRACHER, F., SOHN, K. and SCHALLER, M., 2017. Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion. PLoS One, vol. 12, no. 10, e0184438. http://doi.org/10.1371/journal.pone.0184438. PMid:29023454. http://doi.org/10.1371/journal.pone.0184...
L. rhamnosus GG	OD₆₀₀ of 0.669	C. albicans (SC 5314)	5x10⁶ /mL		Transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans.
Lactobacillus gasseri	Cell-free Supernatants	C. tropicalis	OD₆₀₀ 0.1 or OD₆₀₀ 0.01	Biofilm;	The lactobacilli supernatants reduced the biofilm formation of all non-Candida species.	Tan et al. (2018)TAN, Y., LEONHARD, M., MOSER, D., MA, S. and SCHNEIDER-STICKLER, B., 2018. Inhibitory effect of probiotic lactobacilli supernatants on single and mixed non-albicans Candida species biofilm. Archives of Oral Biology, vol. 85, pp. 40-45. http://doi.org/10.1016/j.archoralbio.2017.10.002. PMid:29031236. http://doi.org/10.1016/j.archoralbio.201...
L. rhamnosus		C. krusei		Cell viability;	Confocal laser scanning microscopy and scanning electron microscopy confirmed that lactobacilli supernatants inhibited the mixed biofilms and damaged the cells.
		C. parapsilosis		Scanning electron microscopy.
L. plantarum SD5870	5x10⁶	C. albicans TIMM 1768	1x10 ⁶ to 1x10⁷ UFC	Biofilm, Candida gene analysis (qPCR)	Combinations of live probiotics or their supernatants reduced biofilm formation of C. albicans.	James et al. (2016)JAMES, K.M., MACDONALD, K.W., CHANYI, R.M., CADIEUX, P.A. and BURTON, J.P., 2016. Inhibition of Candida albicans biofilm formation and modulation of gene expression by probiotic cells and supernatant. Journal of Medical Microbiology, vol. 65, no. 4, pp. 328-336. http://doi.org/10.1099/jmm.0.000226. PMid:26847045. http://doi.org/10.1099/jmm.0.000226...
L. helveticus CBS N116411	Supernatants	C. albicans TIMM 1768	1x10 ⁶ to 1x10⁷ UFC	Biofilm, Candida gene analysis (qPCR)	Supernatants significantly reduced the expression of several C. albicans genes critical to the yeast-hyphae transition, biofilm formation, tissue invasion and cellular damage.

Lactobacillus species	Concentration	Candida species	Concentration	Main Essay	Main Effects	Reference
L. rhamnosus (ATCC 7469)	10⁶ cells/mL	C. albicans	10⁹ cells/mL	Oral candidiasis model in Wistar-immunosuppressed male mice	Groups that consumed probiotics had lower histological and inflammatory infiltrates when compared to the group candidiasis with no probiotic intake.	Leão et al. (2018)LEÃO, M.V.P., TAVARES, T.A.A., GONÇALVES, C.R.S., SANTOS, S.S.F., JUNQUEIRA, J.C., DE OLIVEIRA, L.D. and JORGE, A.O.C., 2018. Lactobacillus rhamnosus intake can prevent the development of Candidiasis. Clinical Oral Investigations, vol. 22, no. 7, pp. 2511-2518. http://doi.org/10.1007/s00784-018-2347-8. PMid:29372447. http://doi.org/10.1007/s00784-018-2347-8...
				(11-12 weeks old);
				Histological evaluation
				Cytokines quantification.

L. paracasei 28.4	10⁶ to 10⁸ cells/mL	C. albicans	10⁸ cells/mL	Oral candidiasis model in Swiss male mice	The 1% probiotic formulation inhibited the growth of C. albicans, prevented the development of candidiasis lesions and suppressed the inflammatory process.	Song and Lee (2017)SONG, Y.G. and LEE, S.H., 2017. Inhibitory effects of Lactobacillus rhamnosus and Lactobacillus casei on Candida biofilm of denture surface. Archives of Oral Biology, vol. 76, pp. 1-6. http://doi.org/10.1016/j.archoralbio.2016.12.014. PMid:28063305. http://doi.org/10.1016/j.archoralbio.201...
L. acidophilus NCFM	10⁹ cells/mL	C. albicans ATCC 90028	10⁸ cells/mL	Oral candidiasis model in DBA/2-immunossuppressed mice (6-8 weeks old)	Probiotics reduced the C. albicans colonization significantly on the oral mucosa in comparison with the untreated animal group. In the group treated with L. rhamnosus, the reduction in yeast colonization was significantly higher compared with that of the group receiving nystatin.	Matsubara et al. (2012)MATSUBARA, V.H., SILVA, E.G., PAULA, C.R., ISHIKAWA, K.H. and NAKAMAE, A.E.M., 2012. Treatment with probiotics in experimental oral colonization by Candida albicans in murine model (DBA/2). Oral Diseases, vol. 18, no. 3, pp. 260-264. http://doi.org/10.1111/j.1601-0825.2011.01868.x. PMid:22059932. http://doi.org/10.1111/j.1601-0825.2011....
L. rhamnosus Lr-32	10⁹ cells/mL	C. albicans ATCC 90028	10⁸ cells/mL
L. rhamnosus L8020	10⁶ cells/mL	C. albicans GDH18	109	Oral candidiasis model in ICR-immunosuppressed female mice (6 weeks old);	Oral consumption of L. rhamnosus L8020 by C. albicans infected mice abolished the pseudomembranous region of the mouse tongue; it also	Ito et al. (2021)ITO, R., MINE, Y., YUMISASHI, Y., YOSHIOKA, R., HAMAOKA, M., TAJI, T., MURAYAMA, T. and NIKAWA, H., 2021. In vivo efficacy of Lacticaseibacillus rhamnosus L8020 in a mouse model of oral candidiasis. Journal of Fungi, vol. 7, no. 5, pp. 322. http://doi.org/10.3390/jof7050322. PMid:33919079. http://doi.org/10.3390/jof7050322...
				Histological evaluation;	significantly reduced the expression levels of Dectin-2 and CCL2, and tended to reduce the expression levels of TLR2 and CXCL1/KC, after infection with C. albicans GDH18.
				RT-PCR (expression of receptors and chemokines)

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