植物乳酸菌LP45株对抗生素诱导肠道菌群、免疫及脑部功能损伤的改善作用

目的 探究益生菌对生命早期抗生素诱导肠道菌群、免疫及脑部功能损伤的改善作用。方法 30只新生小鼠随机分为3组(n=10/组)，分别灌胃灭菌水（对照组）、混合广谱抗生素（抗生素组）、混合广谱抗生素和植物乳酸菌LP45株（LP45组），21d后统一处死。检测血清白介素-6（IL-6），肿瘤坏死因子（TNF-α）和皮质酮；观察肠组织病理学变化；检测海马与前额皮质的部分脑部功能基因mRNA表达情况；对小鼠肠道菌群16s RNA进行分析。结果 抗生素组、LP45组小鼠胸腺体比均低于对照组（F=11.135，P<0.001）；抗生素组、LP45组前额皮质BDNF降低（F=6.921，P=0.005）；抗生素组NGF在前额皮质升高（F=5.921，P=0.014）；LP45组前额皮质GABAAα1（F=12.424，P<0.001）和 GABAB1（F=8.096，P<0.001）低于抗生素组；抗生素组Shannon和Simpson均降低（均P<0.05），LP45组相比抗生素组Simpson升高（P<0.05）；在门水平上抗生素组和LP45组拟杆菌门、厚壁菌门比例下降（均P<0.05），变形菌门比例升高（均P<0.05），在属水平上，LP45组柠檬酸杆菌属比例升高（P<0.05），欧文氏菌属、梭杆菌属、颗粒链菌属、克雷伯氏菌属、奈瑟菌属和链球菌属比例下降（均P<0.05）。结论 生命早期使用抗生素可引起肠道菌群紊乱，植物乳酸菌LP45株对抗生素引起的机体肠道菌群、免疫及脑部功能损伤具有改善作用。

Protective influences of Lactobacillus planatarum LP45 on antibiotic-induced impairment of intestinal microbiota,immunity and brain function

Abstract: Objective To evaluate the influence of antibiotics used in the early life to intestinal microbiota, immunity and brain function of the host animal,and to investigate the protective effects of probiotics against these antibiotic-related damages in the early life to intestinal microbiota, immune and brain functions. Methods Total 30 Kunming neonate mice were randomly divided into the control group, antibiotic group and LP45 group(n=10, respectively), and given sterilized water, mixed broad-spectrum antibiotics and antibiotics combined with Lactobacillus planatarum LP45 strain(LP45 group), respectively since born, and were sacrificed on the 21 st day. The serum interleukin-6(IL-6), tumor necrosis factor(TNF-α) and corticosterone were analyzed, and anatomic pathology changes of small intestine and colon were measured. 16 S RNA next generation sequencing was used for profiling fecal microbiota. Real-time qPCR was used to measure the mRNA expressions of selected brain functional genes in hippocampus and prefrontal cortex. Results The thymus-body ratios in the antibiotic group and LP45 group were lower than that in the control group(F=11.135, P<0.001).mRNA expressions of BDNF of prefrontal cortex were decreased in the antibiotic group and LP45 group(F=6.921, P=0.005), while NGF of prefrontal cortex was increased in antibiotic group(F=5.921, P=0.014). GABAAα1(F=12.424, P<0.001) and GABAB1(F=8.096, P<0.001) of prefrontal cortex in LP45 group were significantly lower than those in antibiotic group. Shannon and Simpson in the antibiotic group were decreased(P<0.01), while Simpson in LP45 group was increased compared with antibiotic group. Shannon and Simpson in the antibiotic group were decreased(P<0.01), while Simpson in LP45 group was increased compared with antibiotic group. There were more Proteobacteria in the antibiotic group and LP45 group, furthermore, less fecal Bacteroides and Firmicutes were found in those two groups. There were more Proteobacteria in the antibiotic group and LP45 group, furthermore, less fecal Bacteroides and Firmicutes were found in those two groups. Compared with the tested mice treated with antibiotics, those fed with LP45 had more fecal Citrobacter Rodentium(P<0.05) and less fecal Erwinia, Fusobacterium, Granulicatella, Klebsiella, Neisseria, Streptococcus(P<0.05).Conclusion The use of antibiotics in early life can cause intestinal flora disorder. LP45 may ameliorate the intestinal flora, immunity and brain function damages caused by antibiotics.