Capsaicin inhibits cariogenic <i>Streptococcus mutans–Candida albicans</i> cross-kingdom biofilms

Objective This research aimed to determine whether capsaicin (CAP), a phytochemical in chilli peppers, inhibits cariogenic Streptococcus mutans–Candida albicans cross-kingdom biofilms and their key virulence factors, and to explore underlying mechanisms.Design The anti-caries potential of CAP was assessed in S. mutans–C. albicans co-cultures by quantifying viable cell counts, biomass and biofilm metabolic activity. Biofilm microstructure was visualized by confocal laser scanning microscopy with COMSTAT quantification, and CAP-induced transcriptional changes were profiled by qRT-PCR. Matched ethanol vehicle controls were included.Results CAP inhibited the growth of both organisms (MIC = 320 µg/mL). At 1/2 MIC (160 µg/mL) and MIC, CAP significantly suppressed biofilm formation, disrupted pre-formed biofilms and decreased acid production and extracellular polysaccharide (EPS) accumulation. In mature biofilms, CAP downregulated key virulence genes associated with EPS biosynthesis (gtfB, gtfC, gtfD) and fungal pathogenicity (HWP1, ERG4, CHT2, SOD3), suggesting potential interference with glucosyltransferase activity, hyphal morphogenesis and membrane-cell wall integrity.Conclusion CAP attenuated key virulence attributes of S. mutans–C. albicans biofilms in vitro, suggesting its potential as a natural adjunct in caries management. However, its efficacy and deliverability require optimization of oral formulations and rigorous in vivo/clinical validation.