Department of Gastroenterology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
Gut Microbes. 2024 Jan-Dec;16(1):2329147. doi: 10.1080/19490976.2024.2329147. Epub 2024 Mar 25.
Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.
C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics.
In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of significantly increased in the IAA treatment group. ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice.
Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.
炎症性肠病（IBD）的特征是肠道的免疫介导的慢性炎症。IBD 的发生是由多种因素的复杂相互作用驱动的。本研究的目的是评估 IAA 在结肠炎中的治疗效果。
C57/BL6 小鼠饮用 2.5% DSS 水诱导结肠炎。IAA 和 R-Equol 通过口服灌胃和常规饮食给药。疾病活动指数用于评估疾病活动度。使用组织学形态、RNA 和炎症标志物蛋白评估结肠炎的严重程度。通过流式细胞术检测 CD45+CD4+FOXP3+Treg 和 CD45+CD4+IL17A+Th17 细胞。使用 16S rRNA 基因测序分析粪便内容物中的肠道微生物组。使用非靶向代谢组学分析肠道微生物组代谢物。
在我们的研究中，我们发现 IAA 通过改变肠道微生物组来缓解 DSS 诱导的小鼠结肠炎。IAA 治疗组中 的丰度显著增加。ATCC25526 通过增加结肠组织中 Foxp3+T 细胞的比例来缓解 DSS 诱导的结肠炎。R-Equol 通过增加 Foxp3+T 细胞来缓解 DSS 诱导的结肠炎，这可能是 ATCC25526 缓解 DSS 诱导的结肠炎的机制之一。
我们的研究表明，吲哚衍生物 IAA 通过促进从 产生 Equol 来缓解 DSS 诱导的结肠炎，这为除经典 AHR 途径以外的吲哚代谢物调节肠道平衡提供了新的见解。
