Probiotic lactic acid bacteria alleviate pediatric IBD and remodel gut microbiota by modulating macrophage polarization and suppressing epithelial apoptosis.

INTRODUCTION

The incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria () can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.

METHODS

For this study, 3-week-old juvenile mice were selected for modeling the development of PIBD. The mice treated with 2% DSS were randomly divided into two groups, which were given CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration . THP-1 and NCM460 cells were used to investigate the effects of CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk .

RESULTS

CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, CECT8330 could inhibit intestinal epithelial apoptosis by suppressing the NF-κB signaling pathway. Meanwhile, it reprogramed macrophages from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype, leading to a decreased secretion of IL-1β which contributes to the reduction in ROS production and epithelial apoptosis. Additionally, the 16S rRNA sequence analysis revealed that CECT8330 could recover the balance of gut microbiota, and a significantly increased content of was particularly observed.

CONCLUSION

CECT8330 shifts macrophage polarization toward an anti-inflammatory M2 phenotype. The decreased production of IL-1β leads to a reduction in ROS, NF-κB activation, and apoptosis in the intestinal epithelium, all of which help to repair the intestinal barrier and adjust gut microbiota in juvenile colitis mice.