PDF(Pubmed)
Abstract：
The prevalence of inflammatory bowel disease (IBD) is rising globally; however, its etiology is still not fully understood. Patient genetics, immune system, and intestinal microbiota are considered critical factors contributing to IBD. Preclinical animal models are crucial to better understand the importance of individual contributing factors. Among these, the dextran sodium sulfate (DSS) colitis model is the most widely used. DSS treatment induces gut inflammation and dysbiosis. However, its exact mode of action remains unclear. To determine whether DSS treatment induces pathogenic changes in the microbiota, we investigated the microbiota-modulating effects of DSS on murine microbiota in vitro. For this purpose, we cultured murine microbiota from the colon in six replicate continuous bioreactors. Three bioreactors were supplemented with 1% DSS and compared with the remaining PBS-treated control bioreactors by means of microbiota taxonomy and functionality. Using metaproteomics, we did not identify significant changes in microbial taxonomy, either at the phylum or genus levels. No differences in the metabolic pathways were observed. Furthermore, the global metabolome and targeted short-chain fatty acid (SCFA) quantification did not reveal any DSS-related changes. DSS had negligible effects on microbial functionality and taxonomy in vitro in the absence of the host environment. Our results underline that the DSS colitis mouse model is a suitable model to study host-microbiota interactions, which may help to understand how intestinal inflammation modulates the microbiota at the taxonomic and functional levels.
摘要：
炎症性肠病（IBD）的患病率在全球范围内呈上升趋势；然而，其病因尚不完全清楚。患者遗传学,免疫系统,和肠道微生物群被认为是导致IBD的关键因素。临床前动物模型对于更好地理解个体影响因素的重要性至关重要。其中,葡聚糖硫酸钠(DSS)结肠炎模型应用最广泛。DSS治疗诱导肠道炎症和生态失调。然而,其确切的作用方式尚不清楚。为了确定DSS治疗是否诱导微生物群的致病性变化，我们在体外研究了DSS对小鼠微生物群的调节作用。为此,我们在六个重复的连续生物反应器中培养了来自结肠的鼠微生物群。用1%DSS补充三个生物反应器,并通过微生物群分类学和功能性与剩余的PBS处理的对照生物反应器进行比较。使用元蛋白质组学，我们没有发现微生物分类学的显著变化，在门或属水平。没有观察到代谢途径的差异。此外，全球代谢组和靶向短链脂肪酸(SCFA)定量未发现任何DSS相关变化.在没有宿主环境的情况下，DSS对体外微生物功能和分类学的影响可以忽略不计。我们的结果强调DSS结肠炎小鼠模型是研究宿主-微生物群相互作用的合适模型。这可能有助于了解肠道炎症如何在分类和功能水平上调节微生物群。
