Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model.
Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model.
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DOI：
10.2147/jir.s358807
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发表时间：
2022
影响因子：
4.5
通讯作者：
中科院分区：
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DSS诱导的UC动物模型已广泛应用于基础研究，肠道菌群失调是DSS诱导UC的重要发病机制之一，但其动态变化及其与炎症因子的相关性尚不清楚。比较不同浓度DSS诱导的C57 BL/6小鼠溃疡性结肠炎模型的临床症状和组织损伤程度，确定DSS的最佳浓度。然后，我们分析了肠道微生物组和炎症因子的测序结果，以确定肠道微生物组的动态模式及其与炎症因子的相关性。2.5%和3.0%浓度的DSS可引起肠道损伤和结肠炎。然而，3.0%DSS导致较高的死亡率。此外，DSS诱导的UC模型中存在肠道微生物组的动态变化：肠道植物群相对丰度在拟杆菌属、副拟杆菌属、Romboutsia、Clostridium_sensu_stricto_1、Lachnospiraceae_NK4A136_group、norank_f_norank_o_Clostridia_UCG-014、Parasutterella中先增加后减少，在乳杆菌属、Muribaculum、norank_f_Muribaculaceae中先减少后增加，双歧杆菌、Coriobacteriaceae_UCG-002和肠杆菌在前14天没有变化，但在第21天显著增加。此外，炎性细胞因子与UC小鼠肠道菌群的失衡密切相关：UC动物模型肠道内大多数致病菌与促炎因子呈正相关，与抗炎因子呈负相关，而有益菌则相反。肠道微生态在DSS诱导的UC模型中起着重要作用，肠道微生物群的相对丰度在溃疡性结肠炎的发生和发展中动态变化。
An animal model of DSS-induced UC has been widely used in basic research, and the dysbiosis of gut microbiome is one of the important pathogenetic mechanisms of DSS-induced UC, but its dynamic changes and correlation with inflammatory factors are not clear yet. Clinical signs and tissue damage degree of C57BL/6 ulcerative colitis mice model induced by different concentrations of DSS were compared with that of normal mice, and finally the optimal concentration of DSS was determined. Then we analyzed the sequencing results of gut microbiome and inflammatory factors to determine the dynamic patterns of gut microbiome and their correlation with the inflammatory factors. DSS at 2.5% and 3.0% concentration could cause intestinal injury and induce colitis. However, 3.0% DSS resulted in higher mortality. In addition, there were dynamic changes of gut microbiome in DSS-induced UC model: the relative abundance of intestinal flora increased first and then decreased in Bacteroides, Parabacteroides, Romboutsia, Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, norank_f_norank_o_Clostridia_UCG-014, Parasutterella, and decreased first and then increased in Lactobacillus, Muribaculum, norank_f_Muribaculaceae, in addition, Bifidobacterium, Coriobacteriaceae_UCG-002 and Enterorhabdus did not change in the first 14 days but increased significantly on day 21. Moreover, inflammatory cytokines were closely associated with the imbalance of the intestinal microbiota in mice with UC: most pathogenic bacteria in the intestinal tract of the UC animal model were positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory factors, while beneficial bacteria were the opposite. Intestinal microecology plays an important role in DSS-induced UC model, and the relative abundance of gut microbiome changes dynamically in the occurrence and development of ulcerative colitis.