Natural Molecules, Nutraceuticals, and Engineered Nanosystems: A Comprehensive Strategy for Combating Gardnerella vaginalis-Induced Bacterial Vaginosis.

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV.