Fermentation-induced metabolic changes and bioactive metabolites in Laminaria japonica fermented by Bacillus subtilis

Laminaria japonica, a brown seaweed, is recognized for its potential health benefits. However, its bioactivity can be limited by poor bioavailability. This research examined the impact of Bacillus subtilis fermentation on the metabolic profile and bioactive properties of L. japonica . Both fermented and unfermented samples were analyzed using untargeted metabolomics and in vitro assays on human umbilical vein endothelial cells (HUVECs). The fermented L. japonica demonstrated an improved capacity to inhibit pro-atherogenic factors in HUVECs, including pro-inflammatory cytokines, chemokines, and adhesion molecules. Post-fermentation, 540 out of 1,665 identified molecules showed significant changes. Up-regulated metabolites included lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds. Pathway analysis identified five significantly enriched metabolic pathways, including amino acid metabolism and glutathione metabolism. Among the up-regulated metabolites, 79 had various bioactivities, mainly antioxidants and anti-inflammatory. Key compounds like pisumoside A, licorice saponin C2, and Bn-NCC-2 increased significantly and can reduce IL-1β secretion. These findings suggest that B. subtilis fermentation enhances L. japonica ’s bioactive properties, especially its anti-inflammatory and antioxidant capabilities. The metabolic changes induced by fermentation could improve anti-atherogenic effects, potentially through direct scavenging of reactive oxygen species and modulation of inflammatory signaling pathways. This study highlights the potential of fermented L. japonica as a functional food ingredient for cardiovascular health. • Metabolic Changes and Bioactive Metabolites after Seaweed Fermentation