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Excessive alcohol consumption is a significant pathogenic factor involved in the initiation of noninfectious gastric ulcers. Probiotics based on a specific strain can mitigate gastric damage. However, the protective effects of Pediococcus acidilactici (GKA4) and Lactobacillus brevis (GKL93) against alcohol-induced gastric mucosal damage remain unclear. Hence, the gastroprotective effects of these probiotic strains were investigated in BALB/c mice with gastric mucosa damage induced by absolute alcohol. The results revealed that preadministration of GKA4 and GKL93 increased the expression of antioxidative enzymes (SOD, catalase, GPx), anti-inflammatory cytokines (IL-4 and IL-10), and heat shock protein genes (HSP70 and HSP90) and decreased the expression of apoptosis-related genes (Bax, cytochrome c, and caspase-3), MDA, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Mechanistically, GKA4 and GKL93 increased the relative abundance of beneficial flora ( Coriobacteriia , Lachnospiraceae_NK4A136_group , Roseburia , f__Oscillospiraceae unclassified , Ruminococcus , Adlercreutzia , and [Eubacterium]_xylanophilum_group ) that may promote antioxidant and anti-inflammatory effects via upregulation of the expression of proteins in the Nrf2/HO-1 pathway and downregulation of the expression of proteins in the NF-κB/iNOS/COX-2 signaling pathway, subsequently attenuating gastrointestinal permeability and ulcer symptoms. Furthermore, correlation analysis revealed that [Eubacterium]_xylanophilum_group and f_Oscillospiraceae_unclassified were two significant beneficial flora associated with ethanol-induced gastric ulcers after preadministration of GKA4 and GKL93. In summary, the gastroprotective effects of P. acidilactici GKA4 and L. brevis GKL93 against ethanol-induced gastric ulcers in mice include suppressing oxidative- and inflammatory-related pathways and modulation of the gut microbiota. This novel finding highlights the potential of these probiotics as functional materials in preventing alcohol-induced gastric mucosal damage.

In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered Lactiplantibacillus plantarum strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-β and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-β and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnan-related gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known anti-inflammatory peptides. Overall, these three L. plantarum strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.