The effect of orthodontic appliances on the Oral Candida colonisation: a systematic review

Candida species is a commensal yeast that colonises the oropharyngeal region of more than 60% of healthy subjects without resulting in clinical symptoms of infection.¹ Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of the Candida species, the most common being Candida albicans.² The ability of Candida to become a pathogenic microorganism is determined by risk factors, including systemic diseases (diabetes or infection) and local factors (orthodontic appliances, removable dentures and poor oral hygiene).² The onset of candidiasis represents a serious clinical problem, especially in immune-compromised patients,³ because the infection can spread via the vascular route or upper gastrointestinal tract and lead to severe systemic infection.² Due to an increase in the use of corticosteroid and immuno-suppressive therapies as well as the improved survival of certain diseases (such as AIDS), an increasing number of immune-compromised patients present for orthodontic treatment, along with their healthy peers.³ Moreover, the number of children diagnosed with cancer is increasing and the greater efficacy of children's oncological treatment has globally increased the number of cancer survivors.⁴ Therefore, the number of oncological children or adolescents seeking orthodontic treatment is also increasing³ and attention must be paid to the possible complications that orthodontic treatment could induce in immuno-compromised patients⁵ as it has been shown that orthodontic appliances (fixed and removable) could promote changes in the oral microbiota.⁶ A Fixed Orthodontic Appliance (FOA) is the most common treatment method used in contemporary orthodontics.⁷ Its complex design based on the fixed placement of brackets and bands can affect oral hygiene practices, thereby promoting the accumulation of dental plaque and altering saliva properties and microbial counts.⁸ A Removable Orthodontic Appliance (ROA) is another common device used to move or retain teeth during or after orthodontic treatment.⁹ Because these acrylic appliances cover a large area of mucosa for extended periods, the prolonged wear of an ROA reduces salivary flow and pH levels, protects the microbiome from the natural flow of saliva and the mechanical removal effects of the oral musculature.⁹ Published literature has shown that these variables would possibly lead to pathogenic Candida colonisation, especially if there are favourable conditions and a reduction in immune function.³ However, the effect of orthodontic treatment by fixed and/or removable appliances on Candida colonisation has not been assessed in an evidence-based manner. The only existing systematic review of treatment-induced Candida changes assessed few databases and found a limited number of studies.³

Therefore, the evaluation of the effects of orthodontic treatment on oral Candida status is helpful for clinicians to decide the most appropriate and individualised treatment based on the patient's clinical conditions, especially in susceptible patients who might have a high risk of local or systemic complications.¹⁰

Therefore, the aim of this review was to evaluate if orthodontic appliances induce changes in Candida colonisation in order to answer the following questions:

Does an orthodontic appliance affect the number and the composition of Candida colonies in the oral cavity?

This systematic review was performed according to the PRISMA statement.¹¹

According to Participants-Intervention-Comparison-Outcome-Study design schema (PICOS), the inclusion and exclusion criteria are summarised in Table I.

The search for articles was carried out using four electronic databases (Pubmed, Scopus, Web of Knowledge, CENTRAL), and included publications in the English language from inception up to September 2021. Human studies which featured the keywords “orthodontic” OR “orthodontics” OR “fixed appliance” OR “removable appliance” OR “bracket” OR “removable aligner” AND “Candida” OR “Candidiasis” OR “Candidosis”, were identified. In addition, the reference and citation lists of the included trials and relevant reviews were manually searched.

All titles identified from the literature were screened and selected by two independent authors (A.C.; E.L.M.). Duplicate studies were eliminated. The abstracts were examined and full texts were obtained if additional data were needed to fulfil the eligibility criteria. Conflicts were resolved by discussion with a third author (L.L.M.).

The characteristics of the included studies (study design, patients, age, orthodontic appliance, sample site, timing, analysis method, outcome, additional measures, quality of the study) were independently extracted by two authors (A.C.; E.L.M.). For further clarification, missing or unclear information was directly requested of the respective authors.

The methodological quality of the included studies was assessed according to the “Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies” (SBU) method.¹² Articles were ranked into three levels (A, B, C) of evidence (Table II) and, based on the score assigned to each study, the review level of available evidence was further scored into four grades (1,2,3,4) (Table III).

Due to the lack of homogeneity in the study setting (study design, sample site, sample collection time and methods), only a systematic review could be conducted rather than a meta-analysis.

The initial search identified 533 articles from Pubmed, Scopus and Web of Knowledge. After eliminating duplicates and ineligible studies by title and abstract, a total of 157 full texts were screened. Finally, a total of sixteen papers were identified according to the eligibility criteria.

The flow chart of the selection of eligible studies for this review is summarised in Figure 1.

Figure 1

According to the SBU tool, the quality of evidence for nine studies was moderate (grade B) and for seven studies was low (grade C). As a result, the level of evidence for the conclusions of this review was considered limited (level 3).

The characteristics of the studies are presented in Table IV. Of the 16 included studies, all were prospective in nature and included four reports which described the changes in Candida in patients treated using a ROA^13,17,20,26 and nine studies which described those treated with FOA.^{8,14,15,16,21,22,23,24,27} Three studies analysed and compared treated and non-treated patients, two of which involved a ROA^17,18 and one used FOA²⁵. An additional untreated group served as a control. Only one study compared the changes in candida between ROA and FOA therapies.¹⁹

The results are summarised in Figure 1.

Arendorf et al.¹³ suggested that ROA may initiate a Candida carrier state by inducing a significant, although transient, increase in Candida colonisation, especially on the palate. According to several studies, an incremental change was found in the Candida counts during ROA therapy, from short^20,26 to a long-term period.²⁰ These results agree with previous studies confirming that ROA wear alters oral microbiological homeostasis due to the presence of new retentive surfaces, the ROA design, and the duration of ROA use, all of which favour bacterial adhesion and biofilm formation.^26,29,30 Mahmoudabi et al.¹⁷ also reported a significant increase in the prevalence of oral colonisation by Candida spp. at a long-term period in ROA patients, compared to untreated controls. Alternative results were reported by Gonçalves et al.¹⁸ who suggested that, although orthodontic treatment may favour the adherence of Candida to epithelial cells, ROA did not influence the presence of yeasts in saliva.

Several studies^8,15,21,22 reported a significant increase in candida colonies during the early stages of FOA treatment, compared to pre-treatment levels. However, contrasting results were reported by earlier studies^16,23,24 in which FOA did not increase the number of Candida carriers during the first few months, while Kouvelis et al.²⁷ failed to identify Candida albicans during FOA therapy. Hägg et al.¹⁴ reported a considerable individual variation in candida counts during the short and the mid-time periods after FOA insertion. A significant increase in candida density on the dorsum of the tongue was found when an imprint culture was used, although the overall prevalence rates of candida obtained using oral saliva and pooled plaque techniques did not demonstrate a change. In contrast, Lee et al.¹⁶ found a significant increase in Candida counts in oral saliva after 5 months of FOA. In a mid-term follow-up, a statistical increase in Candida counts was found in patients with FOA in gargled samples²¹ and dental plaque,^22,25 although Grzegocka et al.²³ reported a non-significant upward trend. Limited studies reported the long-term effect of FOA on Candida density in contrast with two studies which reported a significant increase^15,16 and two other studies reporting non-significant changes.^15,16,21,24 Only one study by Soler et al.²⁴ investigated the candida effects after FOA removal, finding that FOA (both metal and ceramic appliances) did not influence the presence of Candida albicans. Khanpayeh et al.¹⁹ compared the salivary sample of 80 orthodontic subjects, treated with ROA and FOA by dividing subjects into two groups matched by gender and age. A higher frequency of Candida colonisation was found in the FOA group, compared to the ROA group.

It is accepted that the most common aetiological contributor of oral candidiasis is Candida albicans, which causes 45–75% of the total incidence of candidiasis, whereas C. tropicalis, C. glabrata, C. parapsilosis, C. krusei account for about 7% of all cases.²¹

The assessment of candida colonies in orthodontic patients compared to untreated controls showed that Candida albicans was the most prevalent species isolated in both groups, although the method of sampling and analysis differed.^17,18,25

The analysis of the Candida species showed that the most prevalent species in orthodontic patients was C. albicans, while other yeast species were less common during ROA²⁶ and FOA^{14,15,16,21,23,24} treatment. Varying levels of Candida strains were reported among the analysed studies, likely due to individual variability and to the different collection methods.

Furthermore, differences in the oral yeasts of patients with or without orthodontic appliances have demonstrated a higher Candida diversity in the orthodontic group. The wearing of orthodontic appliances significantly increased the tendency for colonisation by multiple yeast species, especially non-albicans species (as C. parapsilosis, C. famata, C. sake, C. glabrata).^{14,15,16,17,18,19,21,23,24,25,26}

A higher colonisation of non-albicans Candida species was also seen in FOA subjects compared with ROA subjects (P = 0.001).¹⁹ The most frequent species in the ROA group was C. albicans (62.5%), while in the FOA group, the frequency of C. albicans was lower (45%) and the frequencies of other species (C. tropicalis, C. parapsilosis, C. Krusei, C. Kefyr) was higher than in the ROA group. Therefore, FOA seemed to promote an increase in the presence of salivary Candida, particularly non-albicans Candida species compared to ROA patients.¹⁹ All of these yeast species have a great ability to form biofilms^23,28 in patients undergoing orthodontic therapy,⁶ mainly in FOA cases.^19,28 Candida strains aggregate or adhere more easily to orthodontic fixed appliances.¹⁶

The increase in Candida species other than C. albicans in FOA patients, may be due to the different environmental conditions of non-albicans Candida strains. After FOA placement, the pH of plaque, the strains and number of micro-organisms in the oral cavity are altered,^{8,14,22,23,27} which allows non-albicans strains to proliferate and adhere more easily to FOA.¹⁶ Moreover, the increased risk of Candida colonisation in orthodontic patients could be attributed to a varying degree of gingival inflammation and mucosal damage that is often seen during orthodontic therapy, and which could have decreased the local defense mechanisms.^20,21 Recent literature²⁸ reported that other local factors, such as mucosal barriers, contributed to the formation of Candida colonies. The first line of defense against the Candida species is an intact mucosa,²⁸ and therefore, there will be an increased risk of infection if there are oral lesions due to local trauma associated with orthodontic appliances.^3,24 It is important to consider that the presence of oral appliances does not appear to increase the clinical signs of candida in individuals who are healthy carriers.³¹ However, Goncalves et al.¹⁸ and Zheng et al.²¹, respectively, reported that the presence of microtrauma of the oral mucosa in orthodontic patients, did not produce candidiasis in the studied patients, despite Candida colonisation.

This situation may be explained by the opportunistic pathogenic character of these micro-organisms, that may cause infection in cases of immuno-suppression. Therefore, clinicians should be cautious when providing orthodontic treatment in immuno-compromised children because of an increased risk of candida infection. This is especially valid during FOA treatment because traumatic mucositis often occurs to the oral mucosa due to FOA irritation throughout treatment.¹⁵

Additional host-dependent variables, such as sialometric variations,^8,13 immuno-deficiency, a diet rich in sugar and deficient oral hygiene,^14,23 should also be considered as contributors to the formation of a Candida spp. biofilm.²⁸

The oral prevention, correct hygiene habits and a greater awareness of children under orthodontic treatment and their parents, not only guarantees the success of treatment, but can also decrease the risk of systemic and/or local diseases, especially in immuno-compromised patients.^{14,19,21,22,23,24,26}