Multi-Omics Insights into the Mechanism of Liver Injury in Dextran Sulfate Sodium-Induced Colitis

Liver injury is a common complication of inflammatory bowel disease (IBD). However, the mechanisms of liver injury development are not clear in IBD patients. Gut microbiota is thought to be engaged in IBD pathogenesis. Here, by an integrated analysis of host transcriptome and colonic microbiome, we have attempted to reveal the mechanism of liver injury in colitis mice. In this study, dextran sulfate sodium (DSS) -induced mice colitis model was constructed. Liver and colon transcriptome results showed that immune response and lipid metabolism-related pathways were dramatically altered, while DNA damage repair-related pathways were only significantly down-regulated in the colon. The microbiota of DSS-treated mice underwent strong transitions. Correlation analyses identified genes associated with liver and colon injury, whose expression was associated with the abundance of liver and gut health-related bacteria Collectively, the results indicate that the liver injury in colitis mice may be related to the intestinal dysbiosis and host-microbiota interactions. These findings may provide new insights for identifying potential targets for the treatment of IBD and its induced liver injury. Twelve 6-week-old C57BL/6 mice were weighed on day 0 of the experiment and randomly divided into control (CON group) and DSS groups (6 per group). The mice in the DSS group drank sterilized water containing 3% DSS (36- 50 kDa; MP Biomedicals, California, USA) ad libitum for 7 consecutive days, and the control group drank sterilized distilled water.肝损伤是炎症性肠病（inflammatory bowel disease, IBD）的常见并发症，但IBD患者肝损伤的发生机制尚未明确。肠道菌群被认为参与了IBD的发病过程。本研究通过对宿主转录组与结肠微生物组进行整合分析，旨在揭示结肠炎小鼠肝损伤的发生机制。本研究构建了葡聚糖硫酸钠（dextran sulfate sodium, DSS）诱导的小鼠结肠炎模型。肝脏与结肠转录组分析结果显示，免疫应答及脂质代谢相关通路发生显著改变，而DNA损伤修复相关通路仅在结肠中显著下调。经DSS处理的小鼠，其肠道菌群发生了显著的群落结构转变。相关性分析筛选出了与肝、结肠损伤相关的基因，这些基因的表达水平与肝脏及肠道健康相关菌群的丰度密切相关。综上，本研究结果表明，结肠炎小鼠的肝损伤可能与肠道菌群失调及宿主-菌群互作有关。本研究结果可为IBD及其诱导的肝损伤的治疗潜在靶点筛选提供新的研究思路。实验第0天，对12只6周龄C57BL/6小鼠进行称重，并随机分为对照组（CON组）与DSS组，每组6只。DSS组小鼠连续7天自由饮用含3% DSS（分子量36~50 kDa；美国加利福尼亚州MP Biomedicals公司）的灭菌水，对照组小鼠则饮用灭菌蒸馏水。