海藻希瓦菌对小鼠结直肠腺瘤发生发展及其免疫微环境的影响OACSTPCD

Objective To investigate the effect of Shewanella algae(S.algae)on the occurrence and development of colorectal adenoma and its regulatory effect on the immune microenvironment in mice.Methods Twenty-four mice were divided into three groups:control group,azoxymethane(AOM)/dextran sodium sulfate(DSS)group,AOM/DSS+S.algae group.The survival status and colorectal adenoma of mice were compared among three groups.Colorectal tissues in the AOM/DSS group and AOM/DSS+S.algae group were collected for high-throughput RNA-seq.Gene set enrichment analysis(GSEA)and cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT)were used to analyze the changes of immune-related pathways,immune cells and immune factors.Results Compared with the AOM/DSS group,the body weight(P＜0.05)and survival rate were decreased,the hematochezia was aggravated,the survival status was worsened,the colorectal length was shortened(all P＜0.05),and the average number and size of adenomas were significantly increased(both P＜0.05)in the AOM/DSS+S.algae group.Compared with the AOM/DSS group,the inflammatory responses were significantly enhanced in AOM/DSS+S.algae group(P＜0.05).The production of pro-inflammatory cytokines including interleukin(IL)-2,IL-6,IL-12,IL-17,interferon(IFN),tumor necrosis factor(TNF)(all P＜0.05)and IL-1β showed an upward trend in the AOM/DSS+S.algae group,while the production of anti-inflammatory cytokines including IL-4,IL-10,IL-13(all P＜0.05)and transforming growth factor β showed an inhibitory trend.Both naive B cells and plasma cells(both P＜0.05)were increased in AOM/DSS+S.algae group,and the nuclear factor-κB(NF-κB)signaling pathway was activated.Conclusion S.algae may form a tumor-promoting immune microenvironment by activating immune signals,such as activation of B cells and activation of the NF-κB pathway,and then promote the development of colorectal adenoma.