AUTHOR=Hua Huiying , Pan Chun , Chen Xixi , Jing Mengxia , Xie Jinfang , Gao Yuanqi , Huang Jiebin , Chen Xuehua , Gao Yujing , Xu Chundi , Li Pu 

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1168924

DOI=10.3389/fmicb.2023.1168924

ISSN=1664-302X

ABSTRACT=<sec><title>Introduction</title><p>The incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria <italic>Pediococcus pentosaceus</italic> (<italic>P. pentosaceus</italic>) can interfere with intestinal immunity, but it is still unknown whether it can alleviate PIBD and the concrete mechanism of immune regulation is unclear.</p></sec><sec><title>Methods</title><p>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 <italic>P. pentosaceus</italic> CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration <italic>in vivo</italic>. THP-1 and NCM460 cells were used to investigate the effects of <italic>P. pentosaceus</italic> CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk <italic>in vitro</italic>.</p></sec><sec><title>Results</title><p><italic>P. pentosaceus</italic> CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, <italic>P. pentosaceus</italic> 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 <italic>P. pentosaceus</italic> CECT8330 could recover the balance of gut microbiota, and a significantly increased content of <italic>Akkermansia muciniphila</italic> was particularly observed.</p></sec><sec><title>Conclusion</title><p><italic>P. pentosaceus</italic> 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.</p></sec>