| Intestinal flora, which are closely related to human health, participate in material metabolism, assist the hosts in nutrition uptake, and synthesize the essential vitamins; besides, the alteration of intestinal flora is associated with various diseases, such as diabetes, gastrointestinal diseases, obesity, cardiovascular diseases or even mental diseases.The composition of microbe is susceptible to a great many factors, for instance, the host genotype, age, diet, and antibiotics. The antineoplastic drugs contain certain toxic and side effects which affect the composition of the intestinal flora; however, the exact mechanism of action is unclear so far. Therefore, the research treats it as the entry point, and attempts to unveil the mechanism of action of howantineoplastic drug Capecitabineaffect the intestinal flora as well as the immune system.The mice are treated as the model in the research, and they are given short-term, medium-term,andlong-termgavage, with the dosage of gavage of 822mg/Kg/day.First of all, we observe the phonotype of the experiment mice and monitor their weight, through which we discover that the weight of mice in the experiment group decreases with withered dorsal seta, indicating that Capecitabine affects the normal intestinal digestion and absorption function of the mice, which is the cause of decreased weight in mice.Secondly, analysis of the flora diversity as well as the structures in the faeces, intestinal content and intestinal mucus at different stages is conducted through 16 srRNA gene sequencing, the results of which show that the dominant flora in the faeces are bacteroidetes and firmicutes; while those in the intestinal content and intestinal mucus are firmicutes, bacteroidetes and proteobacteria. There are significant differences between flora in the faeces and those in the intestinal content and mucus; while those in the intestinal mucus and those in the intestinal content are of high similarity, with no significant differences. Meanwhile, there are differences between flora in the faeces and those in the intestinal content in the experiment group and the control group, but only a few strains show difference. However, the differences of the flora are extremely remarkable between the intestinal mucus in the experiment group and that in the control group. Since intestinal mucus is one of the components of mucosal immunity, it indicates that the intestinal flora are related to the immune system.Finally, we select the differential expression genes as well as their related signal pathways in the experiment group and those in the control group at 3 stages through transcriptome sequencing, followed by further selection of the immune-related differential expression genes together with the signal pathways they are involved. The results of the research discover that, there are 334 differential expression genes in the first-stage experiment group, among which 201 are up-regulation genes, and 133 are down-regulation genes. There are141 differential expression genes in the second-stage experiment group, with 68 up-regulation genes, and 73 down-regulation genes. There are 221 differential expression genes in the third-stage experiment group, with 165 up-regulation genes, and 56 down-regulation genes. There are altogether 25 immune-related differential genes selected during the three stages. The pathways that these immune differential genes are involved include: NOD-like receptor signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, Antigen processing and presentation, Chemokine signaling pathway and Fc gamma R-mediated phagocytosis, among which we discover that the Defa-rs7 is related to the bactericidal effects, while pIg R and CCL28 are associated with the transport and secretion of IgA, respectively, indicating that Capecitabine may affect the mucosal immune system through altering the intestinal flora. |
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