A Behavioral And Brain Histopathological Study On The Changes Of Gut Microbiota In Juvenile Mice

Objective:To describe the effects of ceftriaxone（CTRX）and FMT on the abundance of dominant GM in juvenile mice,and to analyze whether the changes of GM will activate microglia in the brain,so as to influence the development of central CNS,and then show behavioral differences.Background:A large number of studies have shown that the gut microbiota of animal models treated with antibiotics has changed significantly.At the same time,the imbalance of intestinal flora often leads to different degrees of inflammatory response,resulting in different degrees of damage to different collective organs.Fecal microbial transplantation（FMT）is a process of transferring intestinal microbiota from one individual to another.The purpose is to restore the normal microbiota of the intestine,so as to improve or cure the disease.Methods:By feeding CTRX（8g/kg/day）to C57BL/6 mice for 1 week to successfully established a model of dysbiosis.2 weeks of different interventions were used to improve microbiome regulation after the model of dysbiosis was successful establishment:normal saline（NS）,FMT,and Bifid Tripe Viable（BTV）.The control group was fed with normal NS for 3 weeks.GM was analyzed by 16S rRNA sequencing.The learning and memory abilities of mice were evaluated by Morris water maze.At the last,the expression of related markers in the brain was detected by immunohi stochemi stry.Results:1.Ceftriaxone did not affect the weight gain of juvenile mice.2.Intragastric administration of ceftriaxone can change the gut microbiota of juvenile mice.The normal intestinal flora is mainly Firmicutes and Bacteroidetes,and the proportion of them is close to 1.However,the use of ceftriaxone antibiotics will reduce the diversity of intestinal flora and significantly increase the number of Firmicutes in the intestine,mainly enterococci（P<0.05）.3.Ceftriaxone antibiotics can increase the activation of microglia in the central nervous system（P<0.05）,and then reduce the expression level of myelin basic protein（MBP）（P<0.05）.4.Under natural circumstances,gut microbiota has a certain self-healing ability.5.The population abundance of gut microbiota is not invariable,it changed with age.When they were young,they were mainly Firmicutes and Bacteroidetes,and their proportion was basically similar.However,with the increase of age,the percentage of Firmicutes decreased gradually.6.Compared with oral microbial preparations,fecal bacteria transplantation can more effectively help mice establish a perfect flora system.7.The homeostasis of intestinal flora can reduce the number of activated microglia,reduce their inflammatory response,increase the content of MBP,and improve the ability of learning and memory.Conclusions:We found that host microbiota homeostasis is crucial for microglia activation and myelin sheath stability during brain development in juvenile mice,and we provide evidence for a constitutive activity of microbes on the brain’s biological function.