The key Laboratory of Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, China.
Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, United States.
Front Immunol. 2021 Nov 30;12:758227. doi: 10.3389/fimmu.2021.758227. eCollection 2021.
Probiotics are clinically used for diarrhea and inflammatory bowel diseases in both humans and animals. Previous studies have shown that (Ct) protects against intestinal dysfunction, while its regulatory function in the gut needs further investigation and the related mechanisms are still not fully elucidated. This study aims to further verify the protective function of Ct and reveal its underlying mechanisms in alleviating diarrhea and intestinal inflammation. Ct inhibited LPS-induced diarrhea and intestinal inflammation in the ileum. IL-22 was identified and the protective role of Ct in the ileum presented an IL-22-dependent manner according to the transcriptomic analysis and interference mice experiments. The flow cytometric analysis of immune cells in the ileum showed that Ct enhanced the proportions of Th17 cells in response to LPS. The results of hybridization further verified that Ct triggered Th17 cells to produce IL-22, which combined with IL-22RA1 expressed in the epithelial cells. Moreover, Ct was unable to enhance the levels of short-chain fatty acids (SCFAs) in the ileum, suggesting that the protective role of Ct in the ileum was independent of SCFAs. This study uncovered the role of Ct in alleviating diarrhea and inflammation with the mechanism of stimulating Th17 cells in the lamina propria to produce IL-22, highlighting its potential application as a probiotic for diarrhea and inflammation in the ileum.
益生菌在人类和动物的腹泻和炎症性肠病中都有临床应用。之前的研究表明,(Ct)可防止肠道功能障碍,但其在肠道中的调节功能需要进一步研究,相关机制仍未完全阐明。本研究旨在进一步验证 Ct 的保护功能,并揭示其在缓解腹泻和肠道炎症中的潜在机制。Ct 抑制 LPS 诱导的回肠腹泻和炎症。通过转录组分析和干扰小鼠实验,鉴定出了 IL-22,并发现 Ct 通过依赖于 IL-22 的方式在回肠中发挥保护作用。回肠免疫细胞的流式细胞分析表明,Ct 增强了 LPS 反应中 Th17 细胞的比例。杂交的结果进一步验证了 Ct 触发 Th17 细胞产生 IL-22,与上皮细胞中表达的 IL-22RA1 结合。此外,Ct 不能提高回肠中短链脂肪酸(SCFAs)的水平,表明 Ct 在回肠中的保护作用独立于 SCFAs。本研究揭示了 Ct 通过刺激固有层 Th17 细胞产生 IL-22 来缓解腹泻和炎症的作用机制,强调了其作为缓解回肠腹泻和炎症的益生菌的潜在应用。