Selective identification of the herb Picrorhiza kurroa and probiotic Lactobacillus fermentum as a synbiotic with fermentation-enhanced physicochemical, biological, and metabolomic properties

PurposeAlthough secondary metabolites of medicinal plants can modulate the gut microbiota, their prebiotic and synbiotic potential is not fully explored. This study aimed to identify novel medicinal plant-probiotic combination(s) that show prebiotic and synbiotic effects through mutual synergism and reciprocal interactions. MethodsTen Himalayan region medicinal plants were screened for their selective prebiotic efficacy by studying in vitro proliferation of three species of lactic acid bacteria (LAB) and concurrent suppression of E. coli. The top-performing plants were evaluated for synergism with LAB through fermentation of pure extracts, followed by physicochemical, biological, and metabolomic profiling. ResultsAmong the ten plant species, Picrorhiza kurroa (PK) and Adhatoda vasica (AV) exhibited promising prebiotic attributes with PAS scores of 0.50 and 0.44, respectively, while Lactobacillus fermentum (LF) emerged as the most compatible probiotic strain. Unlike AV, fermentation of PK with LF demonstrated superior probiotic growth (2.2-fold increase), elevated total flavonoids (21.6% increase), and improved antioxidant capacity (24.02% increase) compared to unfermented PK. Fermented PK significantly enhanced cytoprotective effects and mitigated oxidative (ROS levels/lipid peroxidation) and inflammatory damage (NO/IL-6 levels) in macrophages and muscle cells exposed to separate exogenous stressors (LPS and H2O2). Elemental (ICP-OES) and metabolomic analysis (LC-MS/UHPLC) revealed that LF metabolised major elements of PK (Ca/Fe/K/Na/Cu) and induced biotransformation of large secondary metabolites, including the characteristic iridoid glycosides of PK, into smaller, more abundant metabolites. ConclusionsPK-LF combination is identified as a synbiotic, and its fermented product is a superior bioactive product that can be developed into innovative nutraceuticals or herbal formulations.