目的:探讨脓毒症小鼠肠道菌群动态变化。方法:选择雄性SPF级C57BL/6小鼠42只，采用盲肠结扎穿孔术（CLP）构建脓毒症模型，按制模后时间分为CLP 6～12 h组（n n＝9）及1、2、3 d组（均n n＝10），并设假手术（Sham）组（n n＝3）。取小鼠结肠腔内粪便进行肠道菌群16S rRNA测序，并对有效序列进行聚类，获得操作分类单元（OTU），用于Alpha多样性分析、物种组成分析、主坐标分析（PCoA分析）和物种差异分析（LEfSe分析），观察CLP后肠道菌群动态变化。n 结果:与Sham组比较，随CLP后时间延长，小鼠肠道菌群Alpha多样性呈下降趋势，表现为群落丰富程度指数降低（CLP后3 d Chao1指数：367.9±162.6比508.3±105.9，Ace指数：372.5±151.9比498.8±104.2），群落多样性指数中Shannon指数降低（CLP后3 d：2.57±1.06比4.30±0.57），Simpson指数升高（CLP后3 d：0.26±0.19比0.04±0.03），提示随CLP后时间延长，肠道菌群丰富程度和多样性均下降。物种组成分析显示，在OTU水平，OTU 633在CLP后1 d时占比最高（24.79%），OTU 1016在CLP后2 d、3 d时占明显优势，CLP后3 d占比最高（61.75%）；在属水平，未标记鼠杆菌的丰度随CLP后时间延长呈先轻度升高后明显下降的趋势，大肠杆菌-志贺菌丰度在CLP后2 d、3 d显著升高，乳杆菌丰度随CLP后时间延长呈先增长后下降趋势，拟杆菌属丰度则随CLP后时间延长呈逐渐升高趋势，提示随CLP后时间延长，小鼠肠道菌群结构发生变化。PCoA分析显示，CLP 6～12 h组菌群结构与Sham组相似度较高，随CLP后时间延长，菌群结构发生变化，CLP 3 d组变化显著。LEfSe分析显示，引起组间差异的主要成分为鼠杆菌科未标记属、普雷沃菌科UCG-001、鼠杆菌科未标记属拟杆菌未定义种、副杆菌、大肠杆菌-志贺菌和OTU 1016。大肠杆菌-志贺菌和OTU 1016在5组样本丰度差异性排名中分别居属水平及OTU水平首位；大肠杆菌-志贺菌丰度从CLP 6～12 h的0.01%（0%，0.02%）随CLP后时间延长而逐渐升高到3 d的44.79%（3.71%，53.75%），OTU 1016的丰度从CLP 6～12 h的0.01%（0%，0.02%）随CLP后时间延长而逐渐升高到3 d的44.69%（3.66%，53.64%）。结论:CLP小鼠存在肠道菌群紊乱，且随着CLP后时间延长，菌群多样性逐渐下降，大肠杆菌-志贺菌逐渐成为绝对优势菌。“,”Objective:To investigate the dynamic changes of intestinal flora in septic model mice.Methods:Forty-two male SPF C57BL/6 mice were selected, the sepsis model was reproduced by cecal ligation and puncture (CLP), and the experimental mice were divided into CLP 6-12 hours group (n n = 9) and 1, 2, 3 days group (all n n = 10) and Sham group (n n = 3) according to the time points after modeling. Intestinal flora 16S rRNA sequencing was carried out within feces from the colonic lumen of mice, and the effective sequences were clustered to obtain an operational classification unit (OTU) for statistical analysis of biological information, including Alpha diversity analysis, species composition analysis, principal coordinate analysis (PCoA analysis) and species difference analysis (LEfSe analysis), the dynamic changes of intestinal flora after CLP modeling were analyzed.n Results:Compared with Sham group, with the prolongation of modeling time, the Alpha diversity of intestinal flora decreased, showing a decrease in community richness index (3 days after CLP: Chao index 1 was 367.9±162.6 vs. 508.3±105.9, Ace index was 372.5±151.9 vs. 498.8±104.2), Shannon index decreased in community diversity index (3 days after CLP: 2.57±1.06 vs. 4.30±0.57, Simpson index increased (3 days after CLP: 0.26±0.19 vs. 0.04±0.03), suggesting that with the progress of CLP modeling time, the richness and diversity of intestinal flora decreased. According to species composition analysis, in OTU level, OTU 633 accounted for the highest proportion in CLP 1 day group (24.79%), OTU 1016 was dominant in CLP 2 days and 3 days groups, and the highest proportion was 61.75% in CLP 3 days group; in genus level, the abundance of n norank_f_Muribaculaceae showed a slight increase and then a significant decrease with time, the abundance of n Escherichia-Shigella increased significantly in CLP 2 days and 3 days groups, the abundance of n Lactobacillus increased first and then decreased with time, the abundance of n Bacteroides showed a trend of gradual increase with time. PCoA analysis suggested that CLP 6-12 hours group had a higher structural similarity with Sham group. The flora structure changed gradually with the time after modeling, and the change was significant after 3 days of CLP. LEfSe analysis indicated that the main components that caused the differences among the groups were gn _norank_f_Muribaculaceae, gn _Prevotellaceae_UCG-001, n s_uncultured_Bacteroidales_bacterium_g_norank_f_Muribaculaceae, n g_Parabacteroides, n Escherichia-Shigella and OTU 1016. The differences in abundance of n Escherichia-Shigella and OTU 1016 among the five groups ranked first in the genus level and OTU level respectively; the abundance of n Escherichia-Shigella gradually increased from 0.01% (0%, 0.02%) in 6-12 hours after CLP to 44.79% (3.71%, 53.75%) in 3 days with time, and the abundance of OTU 1016 increased from 0.01% (0%, 0.02%) in 6-12 hours after CLP to 44.69% (3.66%, 53.64%) in 3 days with time.n Conclusion:Intestinal dysbiosis occurred in all CLP model groups, the diversity of the flora gradually decreased with the progress of modeling time, n Escherichia-Shigella gradually became the dominant bacteria.n