Lactobacillus gasseri JM1 with potential probiotic characteristics alleviates inflammatory response by activating the PI3K/Akt signaling pathway in vitro.

Abstract

Lactobacillus gasseri JM1, a novel strain isolated from infant feces, exhibited common probiotic properties such as high acid tolerance, bile salt tolerance, and adhesion to epithelial Caco-2 cells, suggesting its ability to survive in the gastrointestinal tract and confer potential probiotic action on the host. In the current study, we aimed to evaluate the immunomodulatory activity of L. gasseri JM1 and explore the underlying signaling pathways in vitro. The results showed that pretreatment with L. gasseri JM1 alleviated lipopolysaccharide-induced inflammatory response, as evidenced by downregulation of genes encoding proinflammatory cytokines [IL1B, IL6, IL8, and tumor necrosis factor-α (TNFA)] and upregulation of genes encoding anti-inflammatory cytokines [IL4, IL10, transforming growth factor-β3 (TGFB3), and IFNG]. A high level of gene expression was noted for toll-like receptor 2 and NOD-like receptor 2. Meanwhile, transcriptomic sequencing obtained 84 differentially expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was activated by L. gasseri JM1 in Caco-2 cells. Inhibitor of PI3K/Akt played various roles in the release of cytokines, indicating that the pathway was involved in protecting the host against lipopolysaccharide stress. Moreover, whole-genome sequencing revealed fundamental genetic properties of L. gasseri JM1 and provided clues for probiotic characteristics. In summary, the strain could exert immunomodulatory effects via the toll-like receptor 2 and NOD2-mediated PI3K/Akt signaling pathway and be regarded as a potential probiotic.

Keywords: Lactobacillus gasseri; PI3K/Akt; immunomodulatory activity; probiotic characteristics.