Liang Huijing, Miao Zhonghua, Guo Jiawen, Jiang Fengling, Cheng Ruyue, Shen Xi, Li Ming, He Fang
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China.
Wei Sheng Yan Jiu. 2020 Nov;49(6):873-880. doi: 10.19813/j.cnki.weishengyanjiu.2020.06.001.
To investigate the effects of Lactobacillus on the alleviation and recovery of ceftriaxone-induced intestinal dysbiosis in early life stages of mice, and the possible effect on immunity of the host.
A total of 48 four-week-old Balb/c male mice were randomly divided into four groups, with 12 in each group. The experiment lasted for four weeks. In the first week, mice were given normal saline, ceftriaxone, ceftriaxone plus Lactobacillus rhamnosus GG, ceftriaxone plus direct vat set pickle(PC) by gavage respectively in the control group(ctrl), ceftriaxone group(ceftri), PC group and LGG group. The PC group and LGG group were given PC and LGG respectively for the last three weeks. The feces were collected once a week, and the profile composition of fecal bacteria were analyzed by next-generation sequencing. The mRNA expression levels of interleukin-6(IL-6), IL-12 and tumor necrosis factor α(TNF-α) in the spleen were analysed using quantitative real-time PCR.
In the first week, the simpson index decreased significantly in the ceftri group(P<0. 001), but not in PC and LGG groups. At week four, the observed-species index in the PC group increased significantly(P<0. 001) and the simpson index increased in both LGG group and ceftri group(P<0. 01). As for the flora structure, in the first week, the ctrl group differed from the other three groups significantly(P<0. 05) while no differences were found between the PC group and the LGG group. The firmicutes/bacteroides(F/B) ratio of three ceftriaxone-treated groups increased while the abundance of Akkermansia decreased, particularly in the ceftri group. In the fourth week, the intestinal flora structure were different between four groups(P<0. 05) and the F/B ratio and Akkermansia abundance recovered. Ruminococcaceae, Bacteroidaceae and Tannerellacea appeared in the ceftri group, while Lactobacillus was dominant in the PC group, and Akkermansia was the characteristic species of the LGG group. Weight lost was found in ceftriaxone-treated groups(P<0. 05) and the PC group recovered first. IL-12 and TNF-α mRNA expression of the spleen were lower in PC and LGG groups compared with the ceftri group(P<0. 01). IL-6 mRNA expression level in the LGG group were lower than the ctrl group(P<0. 01).
The administration of antibiotics in the early life stage might inhibit weight gain, reduce the diversity of intestinal flora, damage functional bacteria and cause long-term inflammation, even though self-recovery ability exist. Lactobacillus might be helpful to alleviate the damage of antibiotics. But no therapeutic effect has been found.
探讨乳酸杆菌对小鼠生命早期头孢曲松诱导的肠道菌群失调的缓解和恢复作用，以及对宿主免疫的可能影响。
将48只4周龄雄性Balb/c小鼠随机分为4组，每组12只。实验持续4周。第1周，对照组（ctrl）、头孢曲松组（ceftri）、PC组和LGG组小鼠分别通过灌胃给予生理盐水、头孢曲松、头孢曲松加鼠李糖乳杆菌GG、头孢曲松加直投式发酵剂泡菜（PC）。PC组和LGG组在最后3周分别给予PC和LGG。每周收集一次粪便，通过下一代测序分析粪便细菌的谱组成。使用定量实时PCR分析脾脏中白细胞介素-6（IL-6）、IL-12和肿瘤坏死因子α（TNF-α）的mRNA表达水平。
第1周，头孢曲松组的辛普森指数显著降低（P<0.001），而PC组和LGG组未降低。第4周，PC组的观测物种指数显著增加（P<0.001），LGG组和头孢曲松组的辛普森指数均增加（P<0.01）。至于菌群结构，第1周，ctrl组与其他3组有显著差异（P<0.05），而PC组和LGG组之间未发现差异。三个头孢曲松治疗组的厚壁菌门/拟杆菌门（F/B）比值增加，而阿克曼氏菌的丰度降低，尤其是在头孢曲松组。第4周，4组之间的肠道菌群结构不同（P<0.05），F/B比值和阿克曼氏菌丰度恢复。瘤胃球菌科、拟杆菌科和坦纳菌科出现在头孢曲松组，而PC组中乳酸杆菌占主导，阿克曼氏菌是LGG组的特征物种。头孢曲松治疗组出现体重减轻（P<0.05），PC组最先恢复。与头孢曲松组相比，PC组和LGG组脾脏的IL-12和TNF-α mRNA表达较低（P<0.01）。LGG组的IL-6 mRNA表达水平低于ctrl组（P<0.01）。
生命早期阶段使用抗生素可能会抑制体重增加，降低肠道菌群多样性，损害功能菌并导致长期炎症，即使存在自我恢复能力。乳酸杆菌可能有助于减轻抗生素的损害。但未发现治疗效果。
