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Probiotic lactic acid bacteria alleviate pediatric IBD and remodel gut microbiota by modulating macrophage
Huiying Hua1, Chun Pan1, Xixi Chen1
1Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Insights
Pediococcus pentosaceus CECT8330 alleviates pediatric inflammatory bowel disease (PIBD) by reducing intestinal inflammation and apoptosis. This probiotic shifts immune cells to an anti-inflammatory state and restores gut microbiota balance in juvenile mice.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Pediatric inflammatory bowel disease (PIBD) incidence is rising globally.
- The probiotic Pediococcus pentosaceus (P. pentosaceus) may modulate intestinal immunity, but its role in PIBD is unclear.
Purpose of the Study:
- To investigate the therapeutic potential of P. pentosaceus CECT8330 in a mouse model of PIBD.
- To elucidate the underlying immune regulatory mechanisms of P. pentosaceus CECT8330 in PIBD.
Main Methods:
- PIBD was induced in juvenile mice using DSS; treatment groups received P. pentosaceus CECT8330 or solvent.
- In vivo analysis included fecal and intestinal tissue collection; in vitro studies used THP-1 and NCM460 cells to assess macrophage polarization and epithelial apoptosis.
- Gut microbiota composition was analyzed using 16S rRNA sequencing.
Main Results:
- P. pentosaceus CECT8330 significantly ameliorated PIBD symptoms, improving colon length, spleen size, and intestinal barrier function.
- Mechanistically, it inhibited intestinal epithelial apoptosis via the NF-κB pathway and promoted M2 macrophage polarization, reducing IL-1β secretion.
- Treatment restored gut microbiota balance, notably increasing Akkermansia muciniphila abundance.
Conclusions:
- P. pentosaceus CECT8330 demonstrates therapeutic efficacy in juvenile colitis by modulating macrophage polarization and suppressing inflammatory pathways.
- This probiotic action reduces intestinal epithelial apoptosis and ROS production, thereby repairing the gut barrier and normalizing gut microbiota.
Introduction:
The incidence of pediatric inflammatory bowel disease (PIBD) continues to rise. It was reported that the probiotic lactic acid bacteria Pediococcus 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.
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 P. pentosaceus CECT8330 and equal amounts of solvent, respectively. The feces and intestinal tissue were collected for the mechanism exploration in vivo. THP-1 and NCM460 cells were used to investigate the effects of P. pentosaceus CECT8330 on macrophage polarization, epithelial cell apoptosis, and their crosstalk in vitro.
Results:
P. pentosaceus CECT8330 obviously alleviated colitis symptoms of juvenile mice, including weight loss, colon length shortening, spleen swelling, and intestinal barrier function. Mechanistically, P. pentosaceus 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 P. pentosaceus CECT8330 could recover the balance of gut microbiota, and a significantly increased content of Akkermansia muciniphila was particularly observed.
Conclusion:
P. pentosaceus 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.
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