Department of Gastrointestinal Surgery & Hernia and Abdominal Wall Surgery, the First Hospital, China Medical University, Shenyang, China.
Department of Shenyang Medical Nutrition Clinical Medical Research Center, Shenyang, China.
PLoS Pathog. 2024 Sep 9;20(9):e1012541. doi: 10.1371/journal.ppat.1012541. eCollection 2024 Sep.
Inflammatory bowel disease (IBD) is an immune system disorder primarily characterized by colitis, the exact etiology of which remains unclear. Traditional treatment approaches currently yield limited efficacy and are associated with significant side effects. Extensive research has indicated the potent therapeutic effects of probiotics, particularly Lactobacillus strains, in managing colitis. However, the mechanisms through which Lactobacillus strains ameliorate colitis require further exploration. In our study, we selected Lactobacillus gasseri ATCC33323 from the intestinal microbiota to elucidate the specific mechanisms involved in modulation of colitis. Experimental findings in a DSS-induced colitis mouse model revealed that L. gasseri ATCC33323 significantly improved physiological damage in colitic mice, reduced the severity of colonic inflammation, decreased the production of inflammatory factors, and preserved the integrity of the intestinal epithelial structure and function. It also maintained the expression and localization of adhesive proteins while improving intestinal barrier permeability and restoring dysbiosis in the gut microbiota. E-cadherin, a critical adhesive protein, plays a pivotal role in this protective mechanism. Knocking down E-cadherin expression within the mouse intestinal tract significantly attenuated the ability of L. gasseri ATCC33323 to regulate colitis, thus confirming its protective role through E-cadherin. Finally, transcriptional analysis and in vitro experiments revealed that L. gasseri ATCC33323 regulates CDH1 transcription by affecting NR1I3, thereby promoting E-cadherin expression. These findings contribute to a better understanding of the specific mechanisms by which Lactobacillus strains alleviate colitis, offering new insights for the potential use of L. gasseri as an alternative therapy for IBD, particularly in dietary supplementation.
炎症性肠病（IBD）是一种主要以结肠炎为特征的免疫系统疾病，其确切病因仍不清楚。传统的治疗方法目前疗效有限，且存在显著的副作用。大量研究表明，益生菌，特别是乳杆菌菌株，在治疗结肠炎方面具有强大的治疗效果。然而，乳杆菌菌株改善结肠炎的机制仍需要进一步探索。在我们的研究中，我们从肠道微生物群中选择了干酪乳杆菌 ATCC33323，以阐明其调节结肠炎的具体机制。在 DSS 诱导的结肠炎小鼠模型中的实验结果表明，干酪乳杆菌 ATCC33323 显著改善了结肠炎小鼠的生理损伤，减轻了结肠炎症的严重程度，减少了炎症因子的产生，保持了肠道上皮结构和功能的完整性。它还维持了黏附蛋白的表达和定位，同时改善了肠道屏障通透性，并恢复了肠道微生物群的失调。E-钙黏蛋白是一种关键的黏附蛋白，在这种保护机制中起着关键作用。在小鼠肠道中敲低 E-钙黏蛋白的表达显著减弱了干酪乳杆菌 ATCC33323 调节结肠炎的能力，从而通过 E-钙黏蛋白证实了其保护作用。最后，转录分析和体外实验表明，干酪乳杆菌 ATCC33323 通过影响 NR1I3 来调节 CDH1 的转录，从而促进 E-钙黏蛋白的表达。这些发现有助于更好地理解乳杆菌菌株缓解结肠炎的具体机制，为干酪乳杆菌作为 IBD 的替代治疗方法，特别是在饮食补充方面的潜在用途提供了新的见解。
