Lactic Acid Bacteria-Fermented Natural Products: Mechanisms and Evidence for Ageing- and Stem-Cell-Related Outcomes.

Ageing is driven by chronic inflammation, oxidative stress, and stem cell exhaustion, posing a major global health challenge. Lactic acid bacteria (LAB) fermentation is being investigated as a potential biotechnology to enhance the bioavailability and functionality of natural products, especially polyphenols and bioactive phytochemicals with anti-ageing potential. This review synthesizes recent advances in LAB-fermented natural products and their roles in modulating longevity pathways and stem cell regeneration. LAB fermentation can alter complex plant matrices by releasing or biotransforming substrate-bound phytochemicals and by generating metabolites such as organic acids, peptides, and, in some systems, short-chain fatty acids (SCFAs), cyclic dipeptides (CDPs), or bacterial extracellular vesicles (BEVs); the contribution of each component requires case-specific verification. In cellular and animal models, candidate mechanisms include modulation of nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and AMP-activated protein kinase-sirtuin 1 (AMPK-SIRT1) signaling, although causal active components are often unresolved. Some LAB-fermented preparations or LAB-derived components have been associated with stem-cell-related outcomes in skin, bone, and neural cell or animal models. CDPs and BEVs are candidate fermentation-associated mediators, but evidence for their independent effects on human ageing remains preliminary. Collectively, LAB-fermented natural products are a promising research area for functional foods and nutraceuticals, but their efficacy and safety for ageing-related outcomes require clinical validation. Future research should focus on standardizing fermentation conditions, identifying active metabolites, and validating their clinical efficacy in human studies.