Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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.