IntroductionThe incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteriaPediococcus pentosaceus(P. pentosaceus) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.MethodsFor 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 givenP. pentosaceusCECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism explorationin vivo. THP-1 and NCM460 cells were used to investigate the effects ofP. pentosaceusCECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalkin vitro.ResultsP. pentosaceusCECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically,P. pentosaceusCECT8330 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 thatP. pentosaceusCECT8330 could recover the balance of gut microbiota, and a significantly increased content ofAkkermansia muciniphilawas particularly observed.ConclusionP. pentosaceusCECT8330 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.