Therapeutics and Biotechnology Division, Center for Information-Based Drug Research Korea and Research Institute of Chemical Technology (KRICT), Daejeon, Republic of Korea.
Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, Republic of Korea.
Infect Immun. 2018 Nov 20;86(12). doi: 10.1128/IAI.00091-18. Print 2018 Dec.
Disruption of the healthy intestinal microbiome and homeostasis of the intestinal immune system, which are closely interactive, are two key factors for ulcerative colitis. Here, we show that MI-2, a selective inhibitor of mucosa-associated lymphoid tissue lymphoma translocation-1 (MALT1), alleviated excessive inflammatory responses and was associated with restoration of healthy intestinal microbiome in mice suffering from dextran sulfate sodium (DSS)-induced colitis. We found that the diversity of intestinal microbiome of mice with DSS-induced colitis was significantly lower than that of healthy mice. However, MI-2 treatment in mice with DSS-induced colitis resulted in restored microbially diverse populations. To understand the possibility of the beneficial effect of the restored microbially diverse populations of MI-2-treated mice with DSS-induced colitis, we showed that inserting fecal microbiota from MI-2-treated mice with DSS-induced colitis and healthy control mice into mice with DSS-induced colitis could alleviate symptoms of colitis. The possibility of MI-2 treatment in DSS-induced colitis, associated with restoration of healthy microbially diverse populations in addition to reshaping host immune modulating capacity by reducing inflammatory cytokines (tumor necrosis factor alpha, interleukin-1β [IL-1β], IL-17α, and IL-22), may be considered therapeutic for ulcerative colitis.
健康的肠道微生物组和肠道免疫系统的稳态被破坏，这两者是相互作用的，是溃疡性结肠炎的两个关键因素。在这里，我们表明，MALT1 选择性抑制剂 MI-2 可减轻过度的炎症反应，并与患有葡聚糖硫酸钠（DSS）诱导结肠炎的小鼠恢复健康的肠道微生物组有关。我们发现，DSS 诱导结肠炎小鼠的肠道微生物组多样性明显低于健康小鼠。然而，MI-2 治疗 DSS 诱导结肠炎的小鼠导致微生物多样性得到恢复。为了了解 MI-2 治疗 DSS 诱导结肠炎的恢复微生物多样性的有益效果的可能性，我们表明，将来自 MI-2 治疗的 DSS 诱导结肠炎和健康对照小鼠的粪便微生物群插入 DSS 诱导结肠炎的小鼠中，可以缓解结肠炎的症状。除了通过减少炎症细胞因子（肿瘤坏死因子-α、白细胞介素-1β[IL-1β]、IL-17α和 IL-22）重塑宿主免疫调节能力外，MI-2 治疗 DSS 诱导结肠炎，可能与恢复健康的微生物多样性有关，这可能被认为是溃疡性结肠炎的一种治疗方法。
