Mechanisms of action of Lactobacillus spp. in the treatment of oral candidiasis

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

Abstract

Candida albicans is often associated with oral candidiasis, and drug-resistance profiles have contributed to an increase in morbidity and mortality. It is known that Lactobacillus spp. acts by competing for adhesion to the epithelium, absorption of nutrients and modulation of the human microbiota. Therefore, they are important to assist in the host's microbiological balance and reduce the growth of Candida spp. Until now, there have been no reports in the literature of reviews correlating to the use of Lactobacillus spp. in the treatment of oral candidiasis. Thus, this review aims to highlight the mechanisms of action of Lactobacillus spp. and methods that can be used in the treatment of oral candidiasis. This is a study carried out through the databases PubMed Central and Scientific Electronic Library Online, using the following keywords: Oral Candidiasis and Lactobacillus. Original articles about oral candidiasis were included, with both in vitro and in vivo analyses, and published from 2012 to 2022. Lactobacillus rhamnosus was the most common microorganism used in the experiments against Candida, acting mainly in the reduction of biofilm, filamentation, and competing for adhesion sites of Candida spp. Among in vivo studies, most researchers used immunosuppressed mouse modelsof Candida infection. The studies showed that Lactobacillus has a great potential as a probiotic, acting mainly in the prevention and treatment of mucosal diseases. Thus, the use of Lactobacillus may be a good strategy for the treatment of oral candidiasis.

Keywords:
oral candidiasis; probiotics; Lactobacillus; Candida

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

1. Introduction

The microbiota that colonizes the skin and mucous membranes surfaces are essential to prevent the invasion and colonization of pathogens and protect and defend the organism. The oral cavity comprises a complex microbiota of bacteria, archaea, fungi, viruses, and protozoa. Although fungi are present in lower numbers, Candida spp. is a common and opportunistic pathogen and one of the leading causes of human infections. Worldwide, about 700,000 cases are reported (Sardi et al., 2013; Hillman et al., 2017; Bongomin et al., 2017).

Due to the AIDS (Acquired Immunodeficiency Syndrome) epidemic in the 1980s, interest in oral infections increased, primarily because of the prevalence of oral candidiasis as an opportunistic infection in seropositive individuals (Lewis and Williams, 2017). Imbalances in the oral microbiota favor the proliferation of Candida spp., which leads to oral candidiasis. This pathology can affect all types of patients. However, it is more common in immunocompromised patients, such as those infected with HIV, hepatitis, cancer, or prolonged antimicrobial therapy, and can be fatal if disseminated (Černáková and Rodrigues, 2020; Gheorghe et al., 2021).

Oral candidiasis is a disease whose inflammation of the mucosa can occur under different clinical manifestations, either in the form of acute pseudomembranous candidiasis, acute and chronic erythematous candidiasis, or as chronic hyperplastic candidiasis (Quindós et al., 2019; Williams and Lewis, 2011).

Despite studies describing an increase in the prevalence of oral candidiasis, mainly affecting immunocompromised patients and the elderly, these mycoses remain neglected, with few epidemiological surveillance and insufficient progress in diagnostic and therapeutic methods (Justiz Vaillant and Qurie, 2023; Bessa et al., 2021).

In Brazil, systemic mycoses are not on the national list of notifiable diseases and are not in the routine of epidemiological surveillance. Therefore, there is a lack of epidemiological data on the occurrence, magnitude, and transcendence of infections caused by Candida (Brasil, 2021).

According to the Centers for Disease Control and Prevention (CDC), in 2019, there were 34,800 hospitalizations and 1,700 deaths due to Candida spp. drug-resistance. Of these, 323 cases were related to multidrug-resistant Candida auris (CDC, 2019). Thus, fungal infections are a significant problem for public health (Brown et al., 2012).

Of the 200 species that make up the genus Candida, about 20 are recognized as causing infections (Turner and Butler, 2014; Macêdo et al., 2009). Candida albicans is often associated with oral candidiasis, considered the primary agent of mucosal and systemic infections, in addition to being related to about 70% of infections caused by fungi in the world (Morad et al., 2018). Non-albicans species associated with oral candidiasis include Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei (Mushi et al., 2016). C. glabrata and C. tropicalis are related to high rates of morbidity and mortality (Macêdo et al., 2009; Richardson and Lass‐Flörl, 2008).

C. albicans can have different morphologies, including yeast, pseudohyphae and hypha (Saghrouni et al., 2013). Infection occurs due to several virulence factors, which make fungal colonization successful (Deorukhkar and Roushani, 2017). The yeast should settle in the oral cavity for the disease to establish itself, and this adhesion mechanism is a determining factor for fungal colonization. Furthermore, as host defense factors, salivary flow and swallowing should not completely remove the fungal cells attached to mucosal surfaces (Vila et al., 2020).

Conventional antifungals are used for treatment. However, due to the increase in resistant Candida strains, the effectiveness of these drugs becomes impaired. Thus, searching for new therapies is relevant (Muñoz et al., 2020). Treatment depends on early diagnosis and identification of candidiasis forms, risk factors and the use of suitable antifungal drugs (Garcia-Cuesta et al., 2014).

Currently, four classes of antifungals against Candida are available: polyenes, azoles, echinocandins and 5-flucytosine, a fluorinated cytosine analogue (Bhattacharya et al., 2020). However, drug resistance profiles among pathogenic fungi have increased and contributed to mortality (Muñoz et al., 2020; Ravikumar et al., 2015).

In 2016, the Infectious Diseases Society of America (IDSA) published updated guidelines on treating oral candidiasis (Pappas et al., 2016). One tablet of miconazole 50 mg should be used once a day for seven to fourteen days for mild illness. Alternatively, nystatin may be used four times a day for seven to fourteen days. Oral Fluconazole during this same period should be used in cases of moderate-to-severe oral candidiasis. Despite being widely used for a long time, Fluconazole has still considered a good choice due to its excellent bioavailability, low toxicity, and few adverse effects (Pappas et al., 2016; Quindós et al., 2019). It is important to note that some Candida species are intrinsically resistant to antifungal agents, and Fluconazole's widespread use in prophylaxis has contributed to increasing cases of resistance (Diniz-Neto et al., 2024; Sardi et al., 2013). Furthermore, C. albicans can form biofilms and secrete hydrolytic enzymes that are considered virulence factors (Nicholls et al., 2011).

Thus, it is necessary to develop therapeutic alternatives associated with the use of new antifungal drugs, probiotics and even peptides with antifungal activities (Marcos-Arias et al., 2011). Probiotics are live microorganisms beneficial to the health of their host. The International Scientific Association of Probiotics and Prebiotics (ISAPP) defines products that can be classified as probiotics and prebiotics, and these include medicines, formulas and supplements that benefit human health. The most commonly used strains include Bifidobacterium spp., Lactobacillus spp. and Saccharomyces spp. These probiotics compete for adherence to the epithelium, uptake of nutrients, and modulate the microbiota to modify the microbiological balance of the host and reduce the growth of pathogens, such as Candida spp. (Amara and Shibl, 2015; Hill et al., 2014; Rossoni et al., 2018). In addition, Lactobacillus species secrete products that modulate the expression of C. albicans genes and inhibit biofilm formation (James et al., 2016).

Research with Lactobacillus spp. demonstrate that these bacteria reduce the growth of Candida, inhibit the formation of biofilms, and act on the immune response, stimulating the release of cytokines by macrophages and the expression of pattern recognition receptors in response to C. albicans, which may improve symptoms and invasive infections (Matsubara et al., 2016, 2017). In addition, in the cultivation of Candida with L. rhamnosus, a reduction in the production of proteinase, hemolysis, hyphae and biofilms was observed (Oliveira et al., 2016).

Therefore, it is believed that advances in the use of probiotics in the prevention and treatment of oral candidiasis are an attractive alternative to restoring the microbiota between the bacterial and fungal communities in the oral cavity (Doppalapudi et al., 2020). Thus, our review aims to highlight the mechanisms of action of Lactobacillus spp. and methods used in vitro and in vivo that can be used in the treatment of oral candidiasis.

2. Material and Methods

This is a narrative bibliographic review carried out through the following databases: PubMed Central (PMC) and Scielo (Scientific Electronic Library Online) with the keywords used: Oral Candidiasis AND Lactobacillus. Original articles were included, which had in vitro and in vivo analyses focused on oral candidiasis, in English, published between 2012 and 2022. Articles that did not meet the inclusion criteria were excluded.

During the review, 11 articles focused on oral candidiasis were selected, with analyses performed in vitro and in vivo. However, before discussing the effects of Lactobacillus directly on oral candidiasis, we chose to mention the mechanisms of action of Lactobacillus spp. against Candida spp.

2.1. Mechanisms of action of Lactobacillus spp. against Candida spp.

Recently, a new classification was adopted in the list of prokaryotes with Standing in Nomenclature (LPSN). In this update, Lactobacillus spp. became part of the genus Lactiplantibacillus, which includes Lactobacillus plantarum, Lactobacillus paraplantarum and Lactobacillus pentosus. Lactobacillus casei, considered to be of the genus Lacticaseibacillus, includes Lactobacillus paracasei, and Lactobacillus rhamnosus. The group of Lactobacillus reuteri was called Limosilactobacillus, with the species Lactobacillus reuteri and Lactobacillus vaginalis. Lactobacillus delbrueckii remained in the genus Lactobacillus with the species Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus johnsonii, and the subspecies Lactobacillus delbrueckii, such as Lactobacillus delbrueckii ssp. bulgaricus and L. delbrueckii ssp. (Zheng et al., 2020; ICSP, 2022).

Bacterial and fungal species can occupy the same places on the mucous membranes. However, Lactobacillus may present activities against Candida, preventing fungal infections (Vazquez-Munoz et al., 2022). Lactobacillus spp. are facultative anaerobic, Gram-positive, and catalase-negative microorganisms that can form spores. Their peculiar characteristic is lactic acid production as a product of anaerobic fermentation (Zangl et al., 2020). This acid is commonly reported as a metabolite that inhibits the growth of C. albicans (Ballou et al., 2016). In addition, they present several mechanisms of action, whether in competition for receptors, secretion of metabolic products, or stimulation of the innate and adaptive immune response (Mundula et al., 2019).

Probiotics as adjuvants in therapies are conducive to preventing and reducing symptoms, keeping the microbiota in balance, and improving the immune system, mainly due to their mechanisms that act by helping in mucosal barriers, being antagonistic to pathogens, inhibiting adhesion and invasion of microorganisms, stimulating the immune system, and even the regulation of the central nervous system (Stavropoulou and Bezirtzoglou, 2020).

A recent study demonstrated several antifungal activities of Lactobacillus, in which this genus restricts the progression of chronic periodontitis by inhibiting the secretion of Th17 lymphocytes, which are responsible for the increased production of cytokines that cause an inflammatory process by altering periodontal tissues (Kaźmierczyk-Winciorek et al., 2021).

De Gregorio et al. (2020) showed that L. crispatus BC1 biosurfactants could induce changes in cell morphology, contributing to the inhibition of Candida adhesion to epithelial cells. Thus, the specific action of probiotics against Candida spp. is related to decreased fungal adhesion through coaggregation, biofilm formation, competition for nutrients, and the production of organic acids and antimicrobial substances, such as bacteriocins, acetic acid, biosurfactants, hydrocarbons and hydrogen peroxide (Matsubara et al., 2016; Parolin et al., 2021; Borges et al., 2014; Kovachev, 2018).

2.2. In vitro assays using Lactobacillus spp. against Candida spp. in studies focused on oral candidiasis

Table 1 lists different in vitro tests demonstrating Lactobacillus's performance against Candida spp. The species used were L. acidophilus, L. plantarum, L. paracasei, L. rhamnosus, Lactobacillus fermentum, L. reuteri, L. gasseri, Lactobacillus helveticus, L. casei. We observed that L. rhamnosus was the most commonly used in experiments against Candida. It is worth mentioning that this species is highly genetically characterized (Segers and Lebeer, 2014).

Table 1
In vitro assays using Lactobacillus spp. against Candida spp. in studies focused on oral candidiasis.

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)
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)
		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)
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)
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)
	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)
					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)
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)
L. helveticus CBS N116411	Supernatants				Supernatants significantly reduced the expression of several C. albicans genes critical to the yeast-hyphae transition, biofilm formation, tissue invasion and cellular damage.

Several studies report the antifungal potential of L. rhamnosus, mainly through the reduction of biofilm, filament and adhesion of C. albicans (Allonsius et al., 2017, 2019; Stivala et al., 2021; Ribeiro et al., 2017; Ribeiro et al., 2020). Song and Lee (2017), when testing the action of the probiotics L. rhamnosus GG (ATCC 53103) and L. casei (ATCC 334) on the production of biofilm and hyphae in the resin prosthesis, found that the probiotic association reduced the production of blastoconidia and hyphae of C. albicans without modifying the prosthesis structure. It is known that the transition in yeast-hyphae morphology is paramount for the pathogenicity of Candida species (Witchley et al., 2019).

According to Mailander-Sánchez et al. (2017), the antifungal property of L. rhamnosus GG is mediated by adhesion blocking and nutrient depletion mechanisms. Using oral epithelial cells (Reconstructed Human Oral Epithelium - RHOE), the authors observed that C. albicans in contact with RHOEs stimulates the production of lactate dehydrogenase (LDH) and lysis of epithelial cells. However, when the cells were pre-incubated with the probiotic, there was a reduction in C. albicans and also in the release of LDH, with attenuation of evasion mechanisms and hyphae production.

Lactobacillus spp. modulate the proliferation of pathogens through the production of antimicrobial metabolic by-products, such as biosurfactants (BSs) and bacteriocins (Zheng et al., 2020; Borges et al., 2014). BSs produced by Lactobacillus are reported to have potential effects on Candida adhesion and biofilm formation. An in vitro model of adhesion and biofilm formation using pre-incubation of Lactobacillus species in BSs-sensitized microplates showed that these interfered with C. albicans biofilm formation (Itapary et al., 2019).

Ribeiro et al. (2017) reported that L. rhamnosus down-regulates genes related to filament and adhesion (als3 and hwp1) and transcription (bcr1 and cph1) of C. albicans. When Lactobacillus supernatant was used, Candida metabolism was reduced by about 61%. The same occurred with L. rhamnosus supernatant, which reduced fungal biomass and metabolic activity of single and mixed cultures of Candida. On C. tropicalis, the reduction was 66.84%. For C. krusei, 70.56%, and C. parapsilosis, 41.33%. In mixed cultures of these Candida species on silicone, there was a decrease of 67.16% by L. rhamnosus (Tan et al., 2018).

Rossoni et al. (2018) also evaluated the effect of L. rhamnosus, L. fermentum, and L. paracasei supernatants against C. albicans. The strains L. paracasei 30.1, 37.1, and 39.2 and L. rhamnosus 36.4 had no inhibitory effects on C. albicans ATCC 18804. On the other hand, it is essential to highlight that not all Lactobacillus spp. are beneficial and protective (Kalia et al., 2020). The isolates that showed the highest antifungal activity against C. albicans ATCC 18804 were L. rhamnosus 5.2, L. fermentum 20.4, and L. paracasei 28.4. Although the three strains reduced the expression of the als3, hwp1, cph1 and efg1 genes of C. albicans, L. paracasei showed a better reduction of C. albicans cells and gene expression (Rossoni et al., 2017).

Recently, it was found that L. paracasei 28.4 also interferes with the growth of C. auris (Rossoni et al., 2020), which is quite interesting, given that C. auris is an emerging multidrug-resistant pathogen that causes systemic infections (Jeffery-Smith et al., 2017).

Ribeiro et al. (2020) developed formulations with gellan gum containing L. paracasei 28.4 to improve the availability of the probiotic in the oral cavity. The tested formulations were able to inhibit Candida spp. biofilms, decreasing the total biomass and preventing the formation of hyphae.

A study on the genomic analysis of L. fermentum ATCC 23271 detected genes related to proteins with the ability to tolerate digestive enzymes, bile salts, acid pH, oxidative stress, and the production of lactic acid and host cell adhesion molecules (Santos et al., 2021). In addition, Carmo et al. (2016) observed that L. fermentum ATCC 23271 produces biofilm, co-aggregates and binds to mucin, interacting effectively against C. albicans.

L. acidophilus can co-aggregate with Candida species, with a high rate of coaggregation with C. krusei and C. glabrata being reported. Supernatants from L. acidophilus and L. plantarum have an inhibitory effect on the growth of C. krusei, C. parapsilosis and C. kefyr compared to the antifungal Fluconazole (Salari and Almani, 2020).

Supernatants from L. acidophilus 8MR7 and L. paracasei subspecies paracasei 10MR8 have been shown to inhibit Candida spp. biofilms (Kivanç and Er, 2020). L. acidophilus reduces the growth of C. albicans and decreases the production of hyphae (Vilela et al., 2015).

The supernatant of L. plantarum SD5870 and L. helveticus CBS N116411N considerably reduced the C. albican's adhesion to polyurethane. When the probiotic cells were combined, there was a greater capacity to destroy pre-formed biofilms and decrease the expression of als3, efg1, hwp1 and sap5 genes, related to adhesion, invasion and defenses of C. albicans (James et al., 2016).

Studies by Zeng et al. (2022) corroborate the data presented, since L. plantarum 14917 inhibited the growth of C. albicans under planktonic conditions, as well as the formation of biofilm. L. plantarum strains 8014 and 14917 eliminated cariogenic biofilm formation. When the supernatant of L. plantarum 14917 was tested, there was antibacterial and antifungal activity against C. albicans, but the supernatant of L. plantarum 8014 had bacteriostatic and fungistatic effects.

Parolin et al. (2021) found that L. plantarum was a strong biofilm producer, as was L. gasseri, and provided broad activity against Candida when applied in planktonic media, particularly when exposed to C. lusitaniae SO22 and C. parapsilosis SO27. L. gasseri has also been mentioned as a biofilm inhibitor in mixed cultures of Candida species (Tan et al., 2018).

Jorgensen et al. (2017) analyzing the in vitro efficacy of L. reuteri DSM 17938 and ATCC PTA 5289 against clinical isolates of C. albicans CBS 562 NT, C. dubliniensis 41_3 ZZMK, C. glabrata CBS 863, C. krusei (Issatchenkia orientalis) RV 491, C. parapsilosis 26 PBS and C. tropicalis DSM 7524, and reference isolates of C. albicans CCUG 46390, C. dubliniensis CCUG 48722, C. glabrata CCUG 63819, C. krusei CCUG 56126, C. parapsilosis CCUG 56136 and C. tropicalis CCUG 47037, found that L. reuteri (DSM 17938) exhibited greater coaggregation with C. krusei and had inhibition of Candida strains, except for the two strains of C. krusei. A lower inhibition of C. tropicalis by L. reuteri (DSM 17938) was observed at a concentration of 10⁹ CFU/mL, while C. glabrata was inhibited at the highest concentration.

2.3. In vivo assays using Lactobacillus spp. against Candida spp. in studies focused on oral candidiasis

Most models use immunosuppressed mice for infection by Candida spp. (Table 2). Ito et al. (2021) used mice infected with C. albicans GDH18 to treat L. rhamnosus L8020. The probiotic was effective as the treated group had smaller lesions on their tongues when compared to the control group, administered only in water. The probiotic reduced the expression of Dectin-2 and CCL2 and decreased TLR2 and CXCL1/KC levels.

Table 2
In vivo tests using Lactobacillus spp. against Candida spp. in studies focused on Oral Candidiasis.

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)
				(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)
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)
L. rhamnosus Lr-32
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)
				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)

On the other hand, Leão et al. (2018) used L. rhamnosus ATCC 7469 in their oral candidiasis model by infecting Wistar rats with C. albicans. In the study, probiotics were administered for seven and 21 days to different groups of animals. Ingestion of L. rhamnosus ATCC 7469 for seven days did not significantly influence the CFU count. Meanwhile, C. albicans was not detected in most infected animals that received the probiotic for 21 days.

In the study by Ribeiro et al. (2020) when administering L. paracasei 28.4 in Swiss mice in a 1% probiotic formulation, observed an inhibition of the growth of C. albicans when compared to the control group, preventing the appearance of lesions caused by the candidiasis and inflammation.

Matsubara et al. (2012) used a model of oral candidiasis in DBA/2 mice. It was found that L. acidophilus and L. rhamnosus inhibited yeasts in the oral mucosa. Compared with the control group containing nystatin, it was observed that the drug did not cause a significant reduction in C. albicans, as observed with the group where lactobacilli were administered. Once again, the study points to the importance of new therapeutic methods aimed at oral candidiasis.

Several species of Lactobacillus have probiotic activities that promote intestinal, vaginal and oral health (Mahasneh and Mahasneh, 2017; Vicariotto et al., 2014). However, when focused on oral health, there are few reports in the literature, even though there is evidence that Lactobacillus can decrease the growth of Candida in the human oral cavity (Ishikawa et al., 2015).

The development of probiotic formulations that maintain the viability of the microorganisms and are effective for the consumer is another challenge related to the lack of studies (Fenster et al., 2019). For Chugh and Kamal-Eldin (2020), a probiotic formulation to be considered therapeutic should be in the range of 10⁸ to 10⁹ CFU/g, so that bioavailability, when ingested, is in the range of 10⁶ to 10⁷ CFU/g. It is noticeable that cell viability is necessary and that several mechanisms help maintain the viability of probiotic formulations. Cell inactivation mechanisms are one of the prerequisites (Coutinho et al., 2010).

Gelatin is widely used as a delivery method for probiotics. Gellan gum is a natural polysaccharide commonly used as a food additive and can potentially be manipulated by the pharmaceutical industry to encapsulate Lactobacillus (Coutinho et al., 2010; Ribeiro et al., 2020). However, since the viability of microorganisms is maintained for a short time during their storage, another way to maintain cell viability is to reduce the amount of water available through freezing procedures to allow drying and prolongation of cell viability (Broeckx et al., 2017; Govender et al., 2014). On the other hand, there are complications with liquid formulations since patients do not accept these formulations well due to storage criteria for microbial viability (Vorländer et al., 2020).

Thus, we find that there is a demand to create new mechanisms that protect probiotics, thus improving their shelf life. The application of these microorganisms and their antimicrobial products must be well-validated to have space on the market and not have toxic effects. For this, studying the interactions between microorganisms and the host is crucial.

3. Conclusion

Different fungal genera, such as Candida, Pneumocystis and Cryptococcus, cause morbidity and mortality worldwide. In this context, fungal diseases are advancing, mainly due to their disregard by organ-competent bodies. Therefore, the description of the prevalence of oral candidiasis, its clinical manifestations, and its treatment is of great importance for preserving health, especially when resistance strains to conventional drugs are involved. Thus, it is necessary to search for new therapeutic alternatives for treating oral candidiasis and new probiotic strains and describe their mechanisms of action through in vitro and in vivo studies.

The search for new probiotic strains and mechanisms of action are of great importance. It is known that probiotics are part of the population's daily life and that their benefits are due to the recovery of homeostasis by reducing pathogens, regulating the immune system, and even preventing infections. Therefore, it is expected that new probiotic strains will be able to reduce Candida infection in the oral cavity, as well as the production of its virulence factors, in addition to controlling the inflammatory process resulting from the infection process.

Acknowledgements

The authors thank the Ceuma University, Conselho Nacional de Desenvolvimento Científico e Tecnológico (grant number: 307035/2022-0), and Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (grant number: BEPP 01822/21) for technical and financial support.

References

• ALLONSIUS, C.N., VAN DEN BROEK, M.F.L., DE BOECK, I., KIEKENS, S., OERLEMANS, E.F.M., KIEKENS, F., FOUBERT, K., VANDENHEUVEL, D., COS, P., DELPUTTE, P. and LEBEER, S., 2017. Interplay between Lactobacillus rhamnosus GG and Candida and the involvement of exopolysaccharides. Microbial Biotechnology, vol. 10, no. 6, pp. 1753-1763. http://doi.org/10.1111/1751-7915.12799 PMid:28772020.
  » http://doi.org/10.1111/1751-7915.12799
• ALLONSIUS, C.N., VANDENHEUVEL, D., OERLEMANS, E.F.M., PETROVA, M.I., DONDERS, G.G.G., COS, P., DELPUTTE, P. and LEBEER, S., 2019. Inhibition of Candida albicans morphogenesis by chitinase from Lactobacillus rhamnosus GG. Scientific Reports, vol. 9, no. 1, pp. 2900. http://doi.org/10.1038/s41598-019-39625-0 PMid:30814593.
  » http://doi.org/10.1038/s41598-019-39625-0
• AMARA, A.A. and SHIBL, A., 2015. Role of Probiotics in health improvement, infection control and disease treatment and management. Saudi Pharmaceutical Journal, vol. 23, no. 2, pp. 107-114. http://doi.org/10.1016/j.jsps.2013.07.001 PMid:25972729.
  » http://doi.org/10.1016/j.jsps.2013.07.001
• BALLOU, E.R., AVELAR, G.M., CHILDERS, D.S., MACKIE, J., BAIN, J.M., WAGENER, J., KASTORA, S.L., PANEA, M.D., HARDISON, S.E., WALKER, L.A., ERWIG, L.P., MUNRO, C.A., GOW, N.A., BROWN, G.D., MACCALLUM, D.M. and BROWN, A.J., 2016. Lactate signalling regulates fungal β-glucan masking and immune evasion. Nature Microbiology, vol. 2, no. 2, pp. 16238. http://doi.org/10.1038/nmicrobiol.2016.238 PMid:27941860.
  » http://doi.org/10.1038/nmicrobiol.2016.238
• BESSA, E.R.L., OLIVEIRA, L.D., MUNIZ, A.B., SILVA, G.D.G., FERNANDES, O.C.C. and HERKRATH, F.J., 2021. Epidemiology of oral candidiasis: a household-based population survey in a medium-sized city in Amazonas. Research. Social Development, vol. 10, no. 10, e127101018664. http://doi.org/10.33448/rsd-v10i10.18664
  » http://doi.org/10.33448/rsd-v10i10.18664
• BHATTACHARYA, S., SAE-TIA, S. and FRIES, B.C., 2020. Candidiasis and mechanisms of antifungal resistance. Antibiotics, vol. 9, no. 6, pp. 312. http://doi.org/10.3390/antibiotics9060312 PMid:32526921.
  » http://doi.org/10.3390/antibiotics9060312
• BONGOMIN, F., GAGO, S., OLADELE, R. and DENNING, D., 2017. Global and multi-national prevalence of fungal diseases-estimate precision. Journal of Fungi, vol. 3, no. 4, pp. 57. http://doi.org/10.3390/jof3040057 PMid:29371573.
  » http://doi.org/10.3390/jof3040057
• BORGES, S., SILVA, J. and TEIXEIRA, P., 2014. The role of lactobacilli and probiotics in maintaining vaginal health. Archives of Gynecology and Obstetrics, vol. 289, no. 3, pp. 479-489. http://doi.org/10.1007/s00404-013-3064-9 PMid:24170161.
  » http://doi.org/10.1007/s00404-013-3064-9
• BRASIL. Ministério da Saúde, 2021 [viewed 27 December 2021]. Systemic candidiasis [online]. Available from: http://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/c/candidiase-sistemica
  » http://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/c/candidiase-sistemica
• BROECKX, G., VANDENHEUVEL, D., HENKENS, T., KIEKENS, S., VAN DEN BROEK, M.F., LEBEER, S. and KIEKENS, F., 2017. Enhancing the viability of Lactobacillus rhamnosus GG after spray drying and during storage. International Journal of Pharmaceutics, vol. 534, no. 1-2, pp. 35-41. http://doi.org/10.1016/j.ijpharm.2017.09.075 PMid:28986319.
  » http://doi.org/10.1016/j.ijpharm.2017.09.075
• BROWN, G.D., DENNING, D.W., GOW, N.A., LEVITZ, S.M., NETEA, M.G. and WHITE, T.C., 2012. Hidden killers: human fungal infections. Science Translational Medicine, vol. 4, no. 165, pp. 165rv13. http://doi.org/10.1126/scitranslmed.3004404 PMid:23253612.
  » http://doi.org/10.1126/scitranslmed.3004404
• CARMO, M.S., NORONHA, F.M., ARRUDA, M.O., COSTA, Ê.P., BOMFIM, M.R., MONTEIRO, A.S., FERRO, T.A., FERNANDES, E.S., GIRÓN, J.A. and MONTEIRO-NETO, V., 2016. Lactobacillus fermentum ATCC 23271 displays in vitro inhibitory activities against Candida spp. Frontiers in Microbiology, vol. 7, pp. 1722. http://doi.org/10.3389/fmicb.2016.01722 PMid:27833605.
  » http://doi.org/10.3389/fmicb.2016.01722
• CENTERS FOR DISEASE CONTROL AND PREVENTION – CDC, 2019 [viewed 27 December 2021]. Antibiotic resistance threats in the United States [online]. Available from: https://www.cdc.gov/drugresistance/biggest-threats.html
  » https://www.cdc.gov/drugresistance/biggest-threats.html
• ČERNÁKOVÁ, L. and RODRIGUES, C.F., 2020. Microbial interactions and immunity response in oral Candida species. Future Microbiology, vol. 15, no. 17, pp. 1653-1677. http://doi.org/10.2217/fmb-2020-0113 PMid:33251818.
  » http://doi.org/10.2217/fmb-2020-0113
• CHUGH, B. and KAMAL-ELDIN, A., 2020. Bioactive compounds produced by probiotics in food products. Current Opinion in Food Science, vol. 32, pp. 76-82. http://doi.org/10.1016/j.cofs.2020.02.003
  » http://doi.org/10.1016/j.cofs.2020.02.003
• COUTINHO, D.F., SANT, S.V., SHIN, H., OLIVEIRA, J.T., GOMES, M.E., NEVES, N.M., KHADEMHOSSEINI, A. and REIS, R.L., 2010. Modified Gellan Gum hydrogels with tunable physical and mechanical properties. Biomaterials, vol. 31, no. 29, pp. 7494-7502. http://doi.org/10.1016/j.biomaterials.2010.06.035 PMid:20663552.
  » http://doi.org/10.1016/j.biomaterials.2010.06.035
• DE GREGORIO, P.R., PAROLIN, C., ABRUZZO, A., LUPPI, B., PROTTI, M., MERCOLINI, L., SILVA, J.A., GIORDANI, B., MARANGONI, A., NADER-MACÍAS, M.E.F. and VITALI, B., 2020. Biosurfactant from vaginal Lactobacillus crispatus BC1 as a promising agent to interfere with Candida adhesion. Microbial Cell Factories, vol. 19, no. 1, pp. 133. http://doi.org/10.1186/s12934-020-01390-5 PMid:32552788.
  » http://doi.org/10.1186/s12934-020-01390-5
• DEORUKHKAR, S.C. and ROUSHANI, S., 2017. Virulence traits contributing to pathogenicity of Candida species. Journal of Microbiology & Experimentation, vol. 5, no. 1, pp. 62-65. http://doi.org/10.15406/jmen.2017.05.00140
  » http://doi.org/10.15406/jmen.2017.05.00140
• DINIZ-NETO, H., SILVA, S.L., CORDEIRO, L.V., SILVA, D.F., OLIVEIRA, R.F., ATHAYDE-FILHO, P.F., OLIVEIRA-FILHO, A.A., GUERRA, F.Q.S. and LIMA, E.O., 2024. Antifungal activity of 2-chloro-N-phenylacetamide: a new molecule with fungicidal and antibiofilm activity against fluconazole-resistant Candida spp. Brazilian Journal of Biology = Revista Brasileira de Biologia, vol. 84, e255080. http://doi.org/10.1590/1519-6984.255080
  » http://doi.org/10.1590/1519-6984.255080
• DOPPALAPUDI, R., VUNDAVALLI, S. and PRABHAT, M.P., 2020. Effect of probiotic bacteria on oral Candida in head-and neck-radiotherapy patients: A randomized clinical trial. Journal of Cancer Research and Therapeutics, vol. 16, no. 3, pp. 470-477. http://doi.org/10.4103/jcrt.JCRT_334_18 PMid:32719253.
  » http://doi.org/10.4103/jcrt.JCRT_334_18
• FENSTER, K., FREEBURG, B., HOLLARD, C., WONG, C., RØNHAVE LAURSEN, R. and OUWEHAND, A.C., 2019. The production and delivery of probiotics: a review of a practical approach. Microorganisms, vol. 7, no. 3, pp. 83. http://doi.org/10.3390/microorganisms7030083 PMid:30884906.
  » http://doi.org/10.3390/microorganisms7030083
• GARCIA-CUESTA, C., SARRION-PÉREZ, M.G. and BAGÁN, J.V., 2014. Current treatment of oral candidiasis: a literature review. Journal of Clinical and Experimental Dentistry, vol. 6, no. 5, e576-e582. http://doi.org/10.4317/jced.51798 PMid:25674329.
  » http://doi.org/10.4317/jced.51798
• GHEORGHE, D.C., NICULESCU, A.G., BÎRCĂ, A.C. and GRUMEZESCU, A.M., 2021. Biomaterials for the prevention of oral candidiasis development. Pharmaceutics, vol. 13, no. 6, pp. 803. http://doi.org/10.3390/pharmaceutics13060803 PMid:34072188.
  » http://doi.org/10.3390/pharmaceutics13060803
• GOVENDER, M., CHOONARA, Y.E., KUMAR, P., DU TOIT, L.C., VAN VUUREN, S. and PILLAY, V., 2014. A review of the advancements in probiotic delivery: conventional vs. non-conventional formulations for intestinal flora supplementation. AAPS PharmSciTech, vol. 15, no. 1, pp. 29-43. http://doi.org/10.1208/s12249-013-0027-1 PMid:24222267.
  » http://doi.org/10.1208/s12249-013-0027-1
• HILL, C., GUARNER, F., REID, G., GIBSON, G.R., MERENSTEIN, D.J., POT, B., MORELLI, L., CANANI, R.B., FLINT, H.J., SALMINEN, S., CALDER, P.C. and SANDERS, M.E., 2014. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews. Gastroenterology & Hepatology, vol. 11, no. 8, pp. 506-514. http://doi.org/10.1038/nrgastro.2014.66 PMid:24912386.
  » http://doi.org/10.1038/nrgastro.2014.66
• HILLMAN, E.T., LU, H., YAO, T. and NAKATSU, C.H., 2017. Microbial ecology along the gastrointestinal tract. Microbes and Environments, vol. 32, no. 4, pp. 300-313. http://doi.org/10.1264/jsme2.ME17017 PMid:29129876.
  » http://doi.org/10.1264/jsme2.ME17017
• INTERNATIONAL COMMITTEE ON SYSTEMATICS OF PROKARYOTES – ICSP, 2022 [viewed 21 June 2022]. List of Prokaryotic Names with Position in Nomenclature (LPSN): genus: Lactobacillus [online]. Available from: https://lpsn.dsmz.de/genus/lactobacillus
  » https://lpsn.dsmz.de/genus/lactobacillus
• ISHIKAWA, K.H., MAYER, M.P., MIYAZIMA, T.Y., MATSUBARA, V.H., SILVA, E.G., PAULA, C.R., CAMPOS, T.T. and NAKAMAE, A.E., 2015. A multispecies probiotic reduces oral Candida colonization in denture wearers. Journal of Prosthodontics, vol. 24, no. 3, pp. 194-199. http://doi.org/10.1111/jopr.12198 PMid:25143068.
  » http://doi.org/10.1111/jopr.12198
• ITAPARY, C.S., RAMOS, F.Y., DUARTE, C.L.C., BOMFIM, M.R.Q., OLIVEIRA, B.M., HOLANDA, R.A., SANTOS, V.L., GOMES, M.S., BUOZZI, M.E., SOUZA, M.A., ANDRADE, M.C. and MONTEIRO-NETO, V., 2019. Antifungal and antivirulence activity of vaginal Lactobacillus spp. products against Candida vaginal isolates. Pathogens, vol. 8, no. 3, pp. 150. http://doi.org/10.3390/pathogens8030150 PMid:31547398.
  » http://doi.org/10.3390/pathogens8030150
• 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
• 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
• JEFFERY-SMITH, A., TAORI, S.K., SCHELENZ, S., JEFFERY, K., JOHNSON, E.M., BORMAN, A., MANUEL, R. and BROWN, C.S., 2017. Candida auris: a review of the literature. Clinical Microbiology Reviews, vol. 31, no. 1, e00029-e17. http://doi.org/10.1128/CMR.00029. PMid:29142078.
• 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/10.1080/20002297.2016.1274582
• JUSTIZ VAILLANT, A.A. and QURIE, A., 2023 [viewed 27 December 2023]. Immunodeficiency [online]. Treasure Island: StatPearls. Available from: https://pubmed.ncbi.nlm.nih.gov/29763203/
  » https://pubmed.ncbi.nlm.nih.gov/29763203/
• KALIA, N., SINGH, J. and KAUR, M., 2020. Microbiota in vaginal health and pathogenesis of recurrent vulvovaginal infections: a critical review. Annals of Clinical Microbiology and Antimicrobials, vol. 19, no. 1, pp. 5. http://doi.org/10.1186/s12941-020-0347-4 PMid:31992328.
  » http://doi.org/10.1186/s12941-020-0347-4
• KAŹMIERCZYK-WINCIOREK, M., NĘDZI-GÓRA, M. and SŁOTWIŃSKA, S.M., 2021. The immunomodulating role of probiotics in the prevention and treatment of oral diseases. Central European Journal of Immunology, vol. 46, no. 1, pp. 99-104. http://doi.org/10.5114/ceji.2021.104412 PMid:33897290.
  » http://doi.org/10.5114/ceji.2021.104412
• KIVANÇ, M. and ER, S., 2020. Biofilm formation of Candida Spp. isolated from the vagina and antibiofilm activities of lactic acid bacteria on the these Candida Isolates. African Health Sciences, vol. 20, no. 2, pp. 641-648. http://doi.org/10.4314/ahs.v20i2.12 PMid:33163025.
  » http://doi.org/10.4314/ahs.v20i2.12
• KOVACHEV, S., 2018. Defence factors of vaginal lactobacilli. Critical Reviews in Microbiology, vol. 44, no. 1, pp. 31-39. http://doi.org/10.1080/1040841X.2017.1306688 PMid:28418713.
  » http://doi.org/10.1080/1040841X.2017.1306688
• 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
• LEWIS, M.A.O. and WILLIAMS, D.W., 2017. Diagnosis and management of oral candidosis. British Dental Journal, vol. 223, no. 9, pp. 675-681. http://doi.org/10.1038/sj.bdj.2017.886 PMid:29123282.
  » http://doi.org/10.1038/sj.bdj.2017.886
• MACÊDO, D.P.C., FARIAS, A.M.A., LIMA, N.R.G., SILVA, V.K.A., LEAL, A.F.G. and NEVES, R.P., 2009. Opportunistic yeast infections and enzymatic profile of the etiological agents. Journal of the Brazilian Society of Tropical Medicine, vol. 42, no. 2, pp. 188-191. http://doi.org/10.1590/S0037-8682200900020001. PMid:19448940.
• MAHASNEH, S.A. and MAHASNEH, A.M., 2017. Probiotics: a promising role in dental health. Dentistry Journal, vol. 5, no. 4, pp. 26. http://doi.org/10.3390/dj5040026 PMid:29563432.
  » http://doi.org/10.3390/dj5040026
• 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.0184438
• MARCOS-ARIAS, C., ERASO, E., MADARIAGA, L. and QUINDÓS, G., 2011. In vitro activities of natural products against oral Candida isolates from denture wearers. BMC Complementary and Alternative Medicine, vol. 11, no. 1, pp. 119. http://doi.org/10.1186/1472-6882-11-119 PMid:22118215.
  » http://doi.org/10.1186/1472-6882-11-119
• MATSUBARA, V.H., BANDARA, H.M.H.N., MAYER, M.P. and SAMARANAYAKE, L.P., 2016. Probiotics as antifungals in mucosal candidiasis. Clinical Infectious Diseases, vol. 62, no. 9, pp. 1143-1153. http://doi.org/10.1093/cid/ciw038 PMid:26826375.
  » http://doi.org/10.1093/cid/ciw038
• MATSUBARA, V.H., ISHIKAWA, K.H., ANDO-SUGUIMOTO, E.S., BUENO-SILVA, B., NAKAMAE, A.E. and MAYER, M.P., 2017. Probiotic bacteria alter pattern-recognition receptor expression and cytokine profile in a human macrophage model challenged with Candida albicans and lipopolysaccharide. Frontiers in Microbiology, vol. 8, pp. 2280. http://doi.org/10.3389/fmicb.2017.02280 PMid:29238325.
  » http://doi.org/10.3389/fmicb.2017.02280
• 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.1601-0825.2011.01868.x
• MORAD, H.O., WILD, A.M., WIEHR, S., DAVIES, G., MAURER, A., PICHLER, B.J. and THORNTON, C.R., 2018. Pre-clinical imaging of invasive Candidiasis using ImmunoPET/MR. Frontiers in Microbiology, vol. 9, pp. 1996. http://doi.org/10.3389/fmicb.2018.01996 PMid:30190717.
  » http://doi.org/10.3389/fmicb.2018.01996
• MUNDULA, T., RICCI, F., BARBETTA, B., BACCINI, M. and AMEDEI, A., 2019. Effect of probiotics on oral candidiasis: a systematic review and meta-analysis. Nutrients, vol. 11, no. 10, pp. 2449. http://doi.org/10.3390/nu11102449 PMid:31615039.
  » http://doi.org/10.3390/nu11102449
• MUÑOZ, J.E., ROSSI, D.C., JABES, D.L., BARBOSA, D.A., CUNHA, F.F., NUNES, L.R., ARRUDA, D.C. and TABORDA, C.P., 2020. In vitro and In vivo inhibitory activity of limonene against different isolates of Candida spp. Journal of Fungi, vol. 6, no. 3, pp. 183. http://doi.org/10.3390/jof6030183 PMid:32971732.
  » http://doi.org/10.3390/jof6030183
• MUSHI, M.F., MTEMISIKA, C.I., BADER, O., BII, C., MIRAMBO, M.M., GROß, U. and MSHANA, S.E., 2016. High oral carriage of non-albicans Candida spp. among HIV-infected individuals. International Journal of Infectious Diseases, vol. 49, pp. 185-188. http://doi.org/10.1016/j.ijid.2016.07.001 PMid:27401585.
  » http://doi.org/10.1016/j.ijid.2016.07.001
• NICHOLLS, S., MACCALLUM, D.M., KAFFARNIK, F.A., SELWAY, L., PECK, S.C. and BROWN, A.J., 2011. Activation of the heat shock transcription factor Hsf1 is essential for the full virulence of the fungal pathogen Candida albicans. Fungal Genetics and Biology, vol. 48, no. 3, pp. 297-305. http://doi.org/10.1016/j.fgb.2010.08.010 PMid:20817114.
  » http://doi.org/10.1016/j.fgb.2010.08.010
• OLIVEIRA, V.M.C., SANTOS, S.S.F., SILVA, C.R.G., JORGE, A.O.C. and LEÃO, M.V.P., 2016. Lactobacillus is able to alter the virulence and the sensitivity profile of Candida albicans. Journal of Applied Microbiology, vol. 121, no. 6, pp. 1737-1744. http://doi.org/10.1111/jam.13289 PMid:27606962.
  » http://doi.org/10.1111/jam.13289
• PAPPAS, P.G., KAUFFMAN, C.A., ANDES, D.R., CLANCY, C.J., MARR, K.A., OSTROSKY-ZEICHNER, L., REBOLI, A.C., SCHUSTER, M.G., VAZQUEZ, J.A., WALSH, T.J., ZAOUTIS, T.E. and SOBEL, J.D., 2016. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, vol. 62, no. 4, pp. e1-e50. http://doi.org/10.1093/cid/civ933 PMid:26679628.
  » http://doi.org/10.1093/cid/civ933
• PAROLIN, C., CROATTI, V., LAGHI, L., GIORDANI, B., TONDI, M.R., DE GREGORIO, P.R., FOSCHI, C. and VITALI, B., 2021. Lactobacillus biofilms influence anti-Candida activity. Frontiers in Microbiology, vol. 12, pp. 750368. http://doi.org/10.3389/fmicb.2021.750368 PMid:34777300.
  » http://doi.org/10.3389/fmicb.2021.750368
• QUINDÓS, G., GIL-ALONSO, S., MARCOS-ARIAS, C., SEVILLANO, E., MATEO, E., JAUREGIZAR, N. and ERASO, E., 2019. Therapeutic tools for oral candidiasis: current and new antifungal drugs. Medicina Oral, Patologia Oral y Cirugia Bucal, vol. 24, no. 2, pp. e172-e180. http://doi.org/10.4317/medoral.22978 PMid:30818309.
  » http://doi.org/10.4317/medoral.22978
• RAVIKUMAR, S., WIN, M.S. and CHAI, L.Y., 2015. Optimizing outcomes in immunocompromised hosts: understanding the role of immunotherapy in invasive fungal diseases. Frontiers in Microbiology, vol. 6, pp. 1322. http://doi.org/10.3389/fmicb.2015.01322 PMid:26635780.
  » http://doi.org/10.3389/fmicb.2015.01322
• RIBEIRO, F.C., IGLESIAS, M.C., BARROS, P.P.D., SANTOS, S.S.F., JORGE, A.O.C. and LEÃO, M.P.V., 2017. Lactobacillus rhamnosus interferes with Candida albicans adherence and biofilm formation: a potential alternative treatment of candidiasis. Austin Journal of Pharmacology and Therapeutics, vol. 9, no. 2, pp. 1133. http://doi.org/10.1111/jam.13324
  » http://doi.org/10.1111/jam.13324
• 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 284. 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
• RICHARDSON, M. and LASS‐FLÖRL, C., 2008. Changing epidemiology of systemic fungal infections. Clinical Microbiology and Infection, vol. 14, suppl. 4, pp. 5-24. http://doi.org/10.1111/j.1469-0691.2008.01978.x PMid:18430126.
  » http://doi.org/10.1111/j.1469-0691.2008.01978.x
• ROSSONI, R.D., FUCHS, B.B., DE BARROS, P.P., VELLOSO, M.D., JORGE, A.O., JUNQUEIRA, J.C. and MYLONAKIS, E., 2017. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection. PLoS One, vol. 12, no. 3, e0173332. http://doi.org/10.1371/journal.pone.0173332 PMid:28267809.
  » http://doi.org/10.1371/journal.pone.0173332
• 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/10.1080/08927014.2018.1425402
• ROSSONI, R.D., BARROS, P.P., MENDONÇA, I.D.C., MEDINA, R.P., SILVA, D.H.S., FUCHS, B.B., JUNQUEIRA, J.C. and MYLONAKIS, E., 2020. The postbiotic activity of Lactobacillus paracasei 28.4 against Candida auris. Frontiers in Cellular and Infection Microbiology, vol. 10, pp. 397. http://doi.org/10.3389/fcimb.2020.00397 PMid:32850495.
  » http://doi.org/10.3389/fcimb.2020.00397
• SAGHROUNI, F.B.A.J., ABDELJELIL, J.B., BOUKADIDA, J. and SAID, M.B., 2013. Molecular methods for strain typing of Candida albicans: a review. Journal of Applied Microbiology, vol. 114, no. 6, pp. 1559-1574. http://doi.org/10.1111/jam.12132 PMid:23311504.
  » http://doi.org/10.1111/jam.12132
• 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/10.1080/20002297.2020.1769386
• SANTOS, C.I., CAMPOS, C.D.L., NUNES-NETO, W.R., CARMO, M.S., NOGUEIRA, F.A.B., FERREIRA, R.M., COSTA, E.P.S., GONZAGA, L.F., ARAÚJO, J.M.M., MONTEIRO, J.M., MONTEIRO, C.R.A.V., PLATNER, F.S., FIGUEIREDO, I.F.S., HOLANDA, R.A., MONTEIRO, S.G., FERNANDES, E.S., MONTEIRO, A.S. and MONTEIRO-NETO, V., 2021. Genomic analysis of Limosilactobacillus fermentum ATCC 23271, a potential probiotic strain with anti-Candida activity. Journal of Fungi, vol. 7, no. 10, pp. 794. http://doi.org/10.3390/jof7100794 PMid:34682216.
  » http://doi.org/10.3390/jof7100794
• SARDI, J.C.O., SCORZONI, L., BERNARDI, T., FUSCO-ALMEIDA, A.M. and GIANNINI, M.M., 2013. Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options. Journal of Medical Microbiology, vol. 62, no. 1, pp. 10-24. http://doi.org/10.1099/jmm.0.045054-0 PMid:23180477.
  » http://doi.org/10.1099/jmm.0.045054-0
• SEGERS, M.E. and LEBEER, S., 2014. Towards a better understanding of Lactobacillus rhamnosus GG-host interactions. Microbial Cell Factories, vol. 13, no. 1, suppl. 1, pp. S7. http://doi.org/10.1186/1475-2859-13-S1-S7 PMid:25186587.
  » http://doi.org/10.1186/1475-2859-13-S1-S7
• 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.2016.12.014
• STAVROPOULOU, E. and BEZIRTZOGLOU, E., 2020. Probiotics in medicine: a long debate. Frontiers in Immunology, vol. 11, pp. 2192. http://doi.org/10.3389/fimmu.2020.02192 PMid:33072084.
  » http://doi.org/10.3389/fimmu.2020.02192
• STIVALA, A., CAROTA, G., FUOCHI, V. and FURNERI, P.M., 2021. Lactobacillus rhamnosus AD3 as a promising alternative for probiotic products. Biomolecules, vol. 11, no. 1, pp. 94. http://doi.org/10.3390/biom11010094 PMid:33450875.
  » http://doi.org/10.3390/biom11010094
• 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.2017.10.002
• TURNER, S.A. and BUTLER, G., 2014. The Candida pathogenic species complex. Cold Spring Harbor Perspectives in Medicine, vol. 4, no. 9, pp. a019778. http://doi.org/10.1101/cshperspect.a019778 PMid:25183855.
  » http://doi.org/10.1101/cshperspect.a019778
• VAZQUEZ-MUNOZ, R., THOMPSON, A., RUSSELL, J.T., SOBUE, T., ZHOU, Y. and DONGARI-BAGTZOGLOU, A., 2022. Insights from the Lactobacillus johnsonii genome suggest the production of metabolites with antibiofilm activity against the pathobiont Candida albicans. Frontiers in Microbiology, vol. 13, pp. 853762. http://doi.org/10.3389/fmicb.2022.853762 PMid:35330775.
  » http://doi.org/10.3389/fmicb.2022.853762
• VICARIOTTO, F., MOGNA, L. and DEL PIANO, M., 2014. Effectiveness of the two microorganisms Lactobacillus fermentum LF15 and Lactobacillus plantarum LP01, formulated in slow-release vaginal tablets, in women affected by bacterial vaginosis: a pilot study. Journal of Clinical Gastroenterology, vol. 48, no. 1, suppl. 1, pp. S106-S112. http://doi.org/10.1097/MCG.0000000000000226 PMid:25291116.
  » http://doi.org/10.1097/MCG.0000000000000226
• VILA, T., SULTAN, A.S., MONTELONGO-JAUREGUI, D. and JABRA-RIZK, M.A., 2020. Oral candidiasis: a disease of opportunity. Journal of Fungi, vol. 6, no. 1, pp. 15. http://doi.org/10.3390/jof6010015 PMid:31963180.
  » http://doi.org/10.3390/jof6010015
• VILELA, S.F., BARBOSA, J.O., ROSSONI, R.D., SANTOS, J.D., PRATA, M.C., ANBINDER, A.L., JORGE, A.O. and JUNQUEIRA, J.C., 2015. Lactobacillus acidophilus ATCC 4356 inhibits biofilm formation by C. albicans and attenuates the experimental candidiasis in Galleria mellonella. Virulence, vol. 6, no. 1, pp. 29-39. http://doi.org/10.4161/21505594.2014.981486 PMid:25654408.
  » http://doi.org/10.4161/21505594.2014.981486
• VORLÄNDER, K., KAMPEN, I., FINKE, J.H. and KWADE, A., 2020. Along the process chain to probiotic tablets: evaluation of mechanical impacts on microbial viability. Pharmaceutics, vol. 12, no. 1, pp. 66. http://doi.org/10.3390/pharmaceutics12010066 PMid:31952192.
  » http://doi.org/10.3390/pharmaceutics12010066
• WILLIAMS, D. and LEWIS, M., 2011. Pathogenesis and treatment of oral candidosis. Journal of Oral Microbiology, vol. 3, no. 1, pp. 5771. http://doi.org/10.3402/jom.v3i0.5771 PMid:21547018.
  » http://doi.org/10.3402/jom.v3i0.5771
• WITCHLEY, J.N., PENUMETCHA, P., ABON, N.V., WOOLFORD, C.A., MITCHELL, A.P. and NOBLE, S.M., 2019. Candida albicans morphogenesis programs control the balance between gut commensalism and invasive infection. Cell Host & Microbe, vol. 25, no. 3, pp. 432-443.e6. http://doi.org/10.1016/j.chom.2019.02.008 PMid:30870623.
  » http://doi.org/10.1016/j.chom.2019.02.008
• ZANGL, I., PAP, I.J., ASPÖCK, C. and SCHÜLLER, C., 2020. The role of Lactobacillus species in the control of Candida via biotrophic interactions. Microbial Cell, vol. 7, no. 1, pp. 1-14. http://doi.org/10.15698/mic2020.01.702 PMid:31921929.
  » http://doi.org/10.15698/mic2020.01.702
• ZENG, Y., FADAAK, A., ALOMEIR, N., WU, T.T., RUSTCHENKO, E., QING, S., BAO, J., GILBERT, C. and XIAO, J., 2022. Lactobacillus plantarum disrupts S. mutans–C. albicans cross-kingdom biofilms. Frontiers in Cellular and Infection Microbiology, vol. 12, pp. 872012. http://doi.org/10.3389/fcimb.2022.872012 PMid:35392605.
  » http://doi.org/10.3389/fcimb.2022.872012
• ZHENG, J., WITTOUCK, S., SALVETTI, E., FRANZ, C.M.A.P., HARRIS, H.M.B., MATTARELLI, P., O’TOOLE, P.W., POT, B., VANDAMME, P., WALTER, J., WATANABE, K., WUYTS, S., FELIS, G.E., GÄNZLE, M.G. and LEBEER, S., 2020. A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. International Journal of Systematic and Evolutionary Microbiology, vol. 70, no. 4, pp. 2782-2858. http://doi.org/10.1099/ijsem.0.004107 PMid:32293557.
  » http://doi.org/10.1099/ijsem.0.004107

Publication Dates

• Publication in this collection
  16 Sept 2024
• Date of issue
  2024

History

• Received
  24 Jan 2024
• Accepted
  16 July 2024