Microbiome predictors of candidiasis following corticosteroids in oral lichen planus

Objectives: Topical corticosteroid therapy (TCST) is the primary treatment for oral lichen planus (OLP), but an increased risk of oral candidiasis remains a common adverse effect. This study aimed to identify microbial predictors of candidiasis risk by comparing baseline oral bacteriome and mycobiome profiles of OLP patients who developed candidiasis following TCST with those who did not. Methods: A nested case-control study was conducted among twelve participants from an ongoing randomized controlled trial. Baseline oral rinse samples were collected from symptomatic OLP patients prior to TCST—six who later developed candidiasis (based on clinical and microbiological criteria) at 2–4 weeks post-treatment and six matched controls who did not. Samples were cultured on Sabouraud-dextrose agar with antibiotics to quantify Candida colonization, and DNA was extracted for 16S rRNA and ITS sequencing (Illumina MiSeq) to profile bacterial and fungal communities. Bioinformatics analysis included relative abundance, α-diversity, β-diversity (UNIFRAC), and LEfSe analyses using QIIME2. Results: At baseline, 67% of patients who later developed candidiasis exhibited high Candida colonization compared to 33% in the control group. Both groups showed dominance of Streptococcus and Candida genera; however, the candidiasis group demonstrated significantly lower bacterial α-diversity (Shannon index, p = 0.041), while fungal α-diversity remained similar. Bacterial β-diversity (unweighted UNIFRAC, p = 0.013) differed significantly between groups, but not fungal profiles. LEfSe analysis identified enrichment of Streptococcaceae and several bacterial taxa in the candidiasis group, while distinct bacterial and fungal taxa were enriched among controls. Conclusions: OLP patients who developed oral candidiasis following TCST exhibited lower bacterial diversity and higher baseline Candida colonization before treatment. Specific bacterial taxa, including Streptococcus spp., may serve as potential microbial biomarkers for predicting candidiasis risk. These findings underscore the potential role of the oral microbiome in guiding personalized management strategies for OLP patients receiving corticosteroid therapy.