Hannover Medical School, Institute for Laboratory Animal Science, Hanover, Germany.
Faculty of Medicine, Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
Front Immunol. 2019 Jul 23;10:1708. doi: 10.3389/fimmu.2019.01708. eCollection 2019.
The intestinal microbiota is a complex ecosystem implicated in host health and disease. Inflammatory bowel disease (IBD) is a multifactorial chronic disorder of the gastrointestinal mucosa. Even though the exact mechanisms are still unknown, the intestinal microbiota is crucial in IBD development. We previously showed that murine norovirus (MNV) induces colitis in the -deficient () mouse model of IBD in a microbiota-dependent manner. Thus, in this study we analyzed whether distinct minimal bacterial consortia influence the outcome of MNV-triggered colitis in mice. Gnotobiotic mice associated with Oligo-Mouse-Microbiota 12 (OMM) or Altered Schaedler Flora (ASF) developed little to no inflammatory lesions in the colon and cecum. MNV infection exacerbated colitis severity only in ASF-colonized mice, but not in those associated with OMM. Four weeks after MNV infection, inflammatory lesions in ASF-colonized mice were characterized by epithelial hyperplasia, infiltration of inflammatory cells, and increased barrier permeability. Co-colonization of ASF-colonized mice with segmented filamentous bacteria (SFB) abolished MNV-induced colitis, whereas histopathological scores in SFB-OMM-co-colonized mice stayed unchanged. Moreover, SFB only colonized mice associated with ASF. The SFB-mediated protective effects in ASF-colonized mice involved enhanced activation of intestinal barrier defense mechanisms and mucosal immune responses in the chronic and acute phase of MNV infection. SFB colonization strengthened intestinal barrier function by increasing expression of tight junction proteins, antimicrobial peptides and mucus. Furthermore, SFB colonization enhanced the expression of pro-inflammatory cytokines such as α, β, and , as well as the expression of the regulatory cytokine β. Altogether, our results showed that MNV-triggered colitis depends on the microbial context.
肠道微生物群是一个复杂的生态系统，与宿主的健康和疾病有关。炎症性肠病（IBD）是一种多因素的胃肠道黏膜慢性疾病。尽管确切的机制尚不清楚，但肠道微生物群在 IBD 的发展中起着至关重要的作用。我们之前曾表明，鼠诺如病毒（MNV）在 IBD 的 -缺陷（）小鼠模型中以依赖微生物群的方式诱导结肠炎。因此，在这项研究中，我们分析了不同的最小细菌共生体是否会影响 MNV 引发的结肠炎在 小鼠中的结果。与寡鼠微生物群 12（OMM）或改变的 Schaedler 菌群（ASF）相关联的无菌 小鼠在结肠和盲肠中几乎没有发生炎症病变。MNV 感染仅在 ASF 定植的小鼠中加剧结肠炎的严重程度，但在与 OMM 相关联的小鼠中没有加剧。在 MNV 感染后 4 周，ASF 定植的 小鼠的炎症病变特征为上皮增生、炎症细胞浸润和屏障通透性增加。ASF 定植的 小鼠与分段丝状菌（SFB）共定植消除了 MNV 诱导的结肠炎，而 SFB-OMM 共定植的小鼠的组织病理学评分保持不变。此外，SFB 仅定植与 ASF 相关联的小鼠。在 ASF 定植的小鼠中，SFB 介导的保护作用涉及在 MNV 感染的慢性和急性阶段增强肠道屏障防御机制和黏膜免疫反应。SFB 定植通过增加紧密连接蛋白、抗菌肽和粘液的表达来增强肠道屏障功能。此外，SFB 定植增强了促炎细胞因子如 α、β和 的表达，以及调节细胞因子 β 的表达。总之，我们的结果表明，MNV 触发的结肠炎取决于微生物环境。
