Gastroprotective effects of GKA4 and GKL93 against ethanol-induced gastric ulcers regulation of the immune response and gut microbiota in mice

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. Pediococcus acidilactici GKA4 and Lactobacillus brevis GKL93 exert gastroprotective effects against ethanol-induced gastric ulcers through multiple mechanisms.