Streptococcus salivarius CCFM1416 Modulates Oral Immunity via IL-17/IKBζ and Combats Candida albicans Infection

Oropharyngeal candidiasis (OPC) commonly occurs in immunocompromised individuals, and enhancing endogenous antimicrobial defenses with probiotics has emerged as an effective prevention strategy. Given the critical role of human β-defensin-2 (HBD-2) in combating Candida albicans infection in the oral cavity, this study aimed to identify oral commensal bacteria promoting HBD-2 production in the host. Thirty-five Streptococcus salivarius strains were screened using the HOK-16B cell line, and two were identified as significantly promoting HBD-2 secretion. These strains were further validated in a murine OPC model. The results indicated that oral intervention with S. salivarius CCFM1416 activated the IL-17/IKBζ signaling pathway in the host (IKBζ from 67.73 to 122.27 pg/mg), upregulating the expression of β-defensin (from 13.64 to 25.21 pg/mg). Consequently, C. albicans colonization and adhesion in the oral cavity were markedly reduced. Finally, a 14-day oral toxicity study demonstrated that oral administration of S. salivarius CCFM1416 is safe in vivo. In summary, the research results indicated that S. salivarius CCFM1416 can effectively prevent the occurrence of OPC and is an excellent probiotic candidate for the prevention of oral mucosal infections.