Lactobacillus brevis G‐101 ameliorates colitis in mice by inhibiting NF‐κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2‐like macrophages

Abstract

Aim: We isolated Lactobacillus brevis G-101 from kimchi lactic acid bacteria (LAB) strains, which induced IL-10 expression in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. To evaluate the inflammatory effect of G-101, we examined its inhibitory effect in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice.

Materials and results: The colitic mice were prepared by intrarectal injection of TNBS. We measured intestinal mucosal cytokines by enzyme-linked immunosorbent assay; activation of transcription factors, by immunoblotting; and macrophage polarization markers, by real-time polymerase chain reaction. Of 200 LAB strains tested, Lact. brevis G-101 showed most potent activity for induction of IL-10 expression in LPS-stimulated peritoneal macrophages. However, it significantly inhibited the expression of TNF-α, IL-1β and IL-6 and the phosphorylation of IRAK1 and AKT, and activated NF-κB and MAPKs. Treatment with TNBS caused colon shortening; increased myeloperoxidase activity; and increased IL-1β, IL-6 and TNF-α expression in mice. Oral administration of Lact. brevis G-101 significantly inhibited these activities. Lactobacillus brevis G-101 inhibited TNBS-induced IRAK-1 phosphorylation and NF-κB activation, as well as the expression of COX-2 and iNOS. Lactobacillus brevis G-101 inhibited the expression of M1 macrophage markers, but increased the expression of M2 macrophages in the colons of TNBS-treated mice.

Conclusions: Lactobacillus brevis G-101 may improve colitis by inhibiting the IRAK1/NF-κB, MAPK and AKT pathways and by polarizing M1 macrophages to M2-like macrophages.

Significance and impact of the study: These results suggest that IL-10 expression-inducing LAB can ameliorate colitis by inhibiting NF-κB activation and macrophage polarization.

Keywords: IL-10; Lactobacillus brevis G-101; NF-kB; colitis; macrophage polarization.