该研究主要探讨了乳双歧杆菌V9对头孢曲松钠作用的小鼠肠道菌群的变化。头孢曲松钠连续灌胃5 d建立小鼠肠道菌群失调的模型，然后随机分为4组，分别为模型组及低、中和高剂量组。低、中和高剂量组灌胃不同剂量乳双歧杆菌V9溶液，另设正常对照组，与模型组灌胃等体积生理盐水，连续灌胃23 d。灌胃结束后，采集小鼠的粪便进行活菌计数和16S rDNA测序，检测粪便中微生物组成及分布，测定血清中IL-1β、IL-6、TNF-α以及IL-2的含量，测定小肠及肝脏组织中SOD、MDA、GSH、GSH-Px的含量，HE染色观察小鼠小肠组织病理学变化。结果表明，灌胃乳双歧杆菌V9溶液后，中、高剂量组IL-1β、IL-6、TNF-α及IL-2的含量分别显著降低31.73、17.04、12.57及31.71 pg/mL；高剂量组小肠及肝脏组织中MDA含量显著降低（p<0.01），中、高剂量组SOD、GSH及GSH-Px均极显著升高（p<0.01）。同时，乳双歧杆菌V9使得头孢曲松钠导致的小鼠肠道菌群失调得到明显改善，粪便活菌计数显示高剂量组肠杆菌数量显著降低0.34 lg cfu/g，乳杆菌及双歧杆菌数量显著增加，分别增加0.40 lg cfu/g和0.26 lg cfu/g。拟普雷沃菌属和魏斯氏菌丰度显著降低（p<0.01）。说明乳双歧杆菌V9对由头孢曲松钠引起的肠道菌群失衡具有一定的调节作用，并调节菌群多样性。

Ceftriaxone sodium was intragastrically administered for five days to establish an enteric dysbacteriosis model of mice. Mice were randomly divided into four groups: the model group, and the low-, medium-, and high-dose groups. The low-, medium-, and high-dose groups were intragastrically administered different doses of Bifidobacterium lactis V9 solution, whereas the normal control and model groups were administered the same volume of normal saline. Twenty-three days after administration, the composition and distribution of microorganisms in the feces of the mice were detected using viable count and 16S rRNA gene sequencing. An enzyme-linked immunosorbent assay kit was used to measure the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-2 in serum and the levels of SOD, MDA, GSH, and GSH-Px in the small intestine and liver. HE staining was used to observe the histopathological changes in the small intestine. Thirty days after administration, the levels of IL-1β, IL-6, TNF-α, and IL-2 in the medium- and the high-dose groups were significantly lower than those in the model group (by 31.73, 17.04, 12.57 and 31.71 pg/mL, respectively); the MDA content in the small intestine and liver tissues in the high-dose group was significantly lower than that in the model group (p<0.01). The SOD, GSH, and GSH-Px levels in the middle- and high-dose groups significantly increased (p<0.01). B. lactis V9 significantly ameliorated the intestinal microflora imbalance caused by ceftriaxone sodium in mice. Fecal viable count indicated that the number of Enterobacter spp. significantly reduced (by 0.34 lg CFU/g) in the high-dose group. The numbers of Lactobacillus and Bifidobacterium spp. significantly increased (by 0.40 lg cfu/g and 0.26 lg cfu/g, respectively). The abundance of bacteria in the Alloprevotella and Weissella genera decreased significantly (p<0.01). Thus, B. lactis V9 effectively ameliorated the enteric dysbacteriosis caused by ceftriaxone sodium and regulated the diversity of intestinal microbiota.

国家自然科学基金项目（31870338）；山东省优势学科团队支持计划（2016052410）