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-a, IL-1b and IL-6 and the phosphorylation of IRAK1 and AKT, and activated NF-jB and MAPKs. Treatment with TNBS caused colon shortening; increased myeloperoxidase activity; and increased IL-1b, IL-6 and TNF-a 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-jB 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-jB, 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-jB activation and macrophage polarization.

Lactococcus lactis KR-050L inhibit IL-6/STAT3 activation

“…Cells of Lactobacillus brevis G‐101 induce IL‐10 expression in LPS‐stimulated macrophages, improving colitis by inhibiting the TLR‐4‐linked NF‐kB, MAPK and AKT signalling pathways and polarizing M1 macrophages to M2 macrophages (Jang et al . ). Moreover, the isolated LABs from Gajuknamu kimchi, which is consumed in special regions and seasons, and their inhibitions imply that all of the isolated LABs could be candidate inhibitors of IL‐6/STAT3 activation, but Lc.…”

Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota

“…To date, however, the Lactobacillus species that can be reduced by stressor exposure has not been addressed. Many species of bacteria in the genus Lactobacillus are known to have health promoting effects, and studies from this laboratory, as well as others, indicate that administering probiotic L. reuteri to mice can reduce colonic inflammatory responses [20,21,41]. Because stressor exposure can exacerbate colonic inflammation [42], we focused on whether indigenous L. reuteri was reduced in stressor-exposed animals.…”

The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor

“…Probiotic Lactobacillus-mediated interventions have been shown to downregulate TNF-a in the colon, enhance gut barrier activity, and reduce overall reductions in colitis-related pathology. [46][47][48][49] Additionally, treatment with probiotic Lactobacillus reuteri in mice abrogates the stressor-induced increases in the severity of the inflammatory response to a colonic pathogen. 40 Interestingly, though previous studies have found that Lactobacillus is reduced in the stool, 18,20,21,50 this study showed a reduction in mucosal epithelium-associated Lactobacillus but not in luminal lactobacilli, implying that psychological stressor exposure can have a distinct effects upon groups of mucosal microbiota compared to their luminal counterparts.…”