Determination of Effect of Morus alba Extract and Lactobacillus rhamnosus on Vaginal Microbiota and SAP Gene (1–10) Profile With Candida albicans Exosome Administration in Rats

Vaginal microbiota is essential for mucosal immunity, pathogen defense, and homeostasis. Disruption of this balance can promote opportunistic infections, notably by Candida albicans. This study investigates the therapeutic potential of Morus alba (MA) extract and Lactobacillus rhamnosus (LR) in a rat model exposed to Candida albicans exosomes (CAE). CAE induced a 1.3–5.1-fold upregulation in SAP1–10 gene expression, with SAP4 showing the highest increase (p ≤ 0.05). MA and LR monotherapies selectively suppressed SAP6 (41%) and SAP4 (23%), respectively. Notably, combination therapy (CAE+MA+LR) synergistically inhibited all SAP genes (0.8–1.1-fold, p ≤ 0.05). 16S rRNA analysis showed that LR-containing groups maintained Lactobacillales abundance (37.77%–38.7%), while MA reduced Mycobacteriales by 68.5% (p = 0.004). Microbial diversity was lower in the MA group (H = 3.242) but higher in LR groups (H = 5.493–5.598). Histopathology revealed severe ovarian inflammation in the CAE group (87.4%, p = 0.0022) with a 4.2-fold increase in IL-6, while combination therapy reduced inflammation and IL-6 levels by 60%–72% (p ≤ 0.05). Immunofluorescence confirmed downregulation of TLR4 and Caspase-3 with treatment. FIB-SEM and NTA analyses showed that CAE exosomes had a heterogeneous morphology (99.3 ± 31.1 nm) and high polydispersity (PDI = 0.31). These results suggest that MA and LR synergistically reduce fungal virulence, restore microbial balance, and offer a promising adjuvant strategy against vaginal candidiasis. © 2025 The Author(s). MicrobiologyOpen published by John Wiley & Sons Ltd.