Short Chain Fatty Acids Protect Brain Development In Gut Dysbiosis Mice Model

Background An increasing research defines humans and their gut microbiota as a whole,the communications among the whole goes beyond the gut.Gut microbiota has been linked to liver disease,allergies,diabetes,autoimmune arthritis,and even neurological disorders.The gut microbiota is crucial in regulating brain function.As brain development rapidly during early life,neonatal gut dysbiosis during early colonization can alter normal brain development by dysregulating immune responses and neuronal differentiation.Short-chain fatty acids are metabolites of gut microbiota,which are vital to the body function of host health and nutrition.Given the clinical treatment of the widespread use of antibiotics in premature infants,microbiota dysbiosis caused by antibiotics in the newborn on the influence of the gut-brain axis（MGB）development and the role of the short-chain fatty acids is worth studying.Objective This study established the microbiota dysbiosis models by antibiotic administration in 7-day mice.Then the bifidobacterium and fecal bacteria liquids were administered to help rebuild the micro intestinal ecology.To explore the role of shortchain fatty acids,the study compard the abundance of short-chain fatty acids in different periods fecal,the cognitive function among all groups,and brain tissue protein expressions in newborn mice microbiota dysbiosis model.Methods The entire forty 7day-C57BL/6J mice were randomly separated into four groups: three of them are antibiotic groups,the other group is the control group.The mice of antibiotic groups oral antibiotic（ceftriaxone）by gavage twice daily for 7days.The control group mice oral vehicle（water）by gavage twice.On the 8th day,antibiotic groups were divided into three different gut-microbiota-intervention groups for the 14-days intervention stage: Bifidobacterium transplantation group,fecal microbiota transplantation group,and negative group-vehicle（water）intervention.Finally,all mice were euthanized after the completion of behavioral testing.Fecal pellets were collected on the 1st day,7th day,and 21 st day for 16 S Illumina sequencing and Liquid Chromatography-mass spectrometry（LC-MS）.Brain tissues from these mice were collected for western blot（WB）and immunohistochemistry（IHC）.Results Gut dysbiosis appeared following antibiotic administration.Expressions of brain markers proteins（IBA1 and MBP）significantly decreased in gut dysbiosis mice,and gut microbiota rebuild interventions could remit the altered situation.Brain function disorders were confirmed by MWM,demonstrating cognitive and learning deficits in neonatally dysbiosis mice compared to the control group.Meanwhile,as the intestinal microecology regained,levels of SCFAs rose,which decreased during the neonatal dysbiosis stage.Conclusions The impact of neonatal dysbiosis on the MGB axis potentially contributes to impaired cognitive function and impeded nervous system development.SCFAs play a vital role in this altered phenotype as guardians.