期刊
THERANOSTICS
卷 10, 期 23, 页码 10665-10679出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.43528
关键词
Rhein; DSS-induced colitis; purine metabolism; uric acid; gut microbiota
资金
- National Natural Science Foundation of China [81961128020, 81973587, 81673725, 81973734, 81673648, 81673795]
- Jiangsu Province Traditional Chinese Medicine Leadi ng Talents Program [SLJ0229]
- Natural Science Foundation of Higher School of Jiangsu Province [17KJA360003, 18KJA360007]
- Natural Science Foundation of Jiangsu Province [BK20151567]
- Jiangsu College graduate research and innovation projects [KYCX17_1315]
- 2013 Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education
- Flagship Major Development of Jiangsu Higher Education Institutions [PPZY2015A070]
Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据