The Study Of Alleviation Effects On Depression-like Symptoms In Mice By Four Species Of Lactobacillus

Major depressive disorder(MDD)is a common mood disorder.Patients are continuously depressed,pessimistic,frequently insomnia,suffering from mental pain,and sometimes accompanied by physical symptoms.There are about 350 million patients with depression in the world.Depression is one of the main causes of the global disease burden.At present,medicines for depression may be accompanied by inevitable side effects,such as nausea,vomiting and diarrhea.Diet,infection,disease and other factors will affect the gut microbiota.Abnormal microbiota can change the behavior,immunity and endocrine of the host.The core processes of gut microbiota affecting the nervous system include neurogenesis,synaptic plasticity,neurotransmitter signals,neurodevelopment and neuroinflammation.The abnormalities of gut microbiota are significantly associated with autism spectrum disorders,depression and Parkinson’s disease.Dietary regulation for regulating gut microbiota is a new way to alleviate mood disorders.Some probiotics show good anti-anxiety and antidepressant effects,including the regulation of neurotransmission,inflammation,hypothalamus-pituitary-adrenal(HPA)axis function and gut microbiota.Previous studies have shown that a considerable part of probiotics that can alleviate depression like symptoms are Lactobacillus.Here,we used the depression mouse model constructed by chronic unpredictable stress(CUS)to evaluate the antidepressant effect of 13 strains of Lactobacillus through behavioral test.In this study,the neurobiological indexes and purine metabolism indexes related to depression were measured.The changes of gut microbiota were analyzed and the function of it was predicted.Through correlation analysis,the relationship between Lactobacillus,gut microbiota,purine metabolism and depression were constructed,in order to provide theoretical support for the development of mental probiotics.The main research contents and results are as follows:(1)Using CUS depression model,13 strains of Lactobacillus were used to intervene in depression experimental rats.The antidepressant effects of Lactobacillus strains were evaluated through five behavioral(forced swimming,tail suspension,open field,marble burying,light/dark box test)and biochemical indexes(brain 5-HT,serum CORT and hippocampal BDNF levels).Three strains of Lactobacillus with excellent antidepressant function were screened,namely Lactobacillus paracasei 126L6,L.paracasei CCFM1229 and L.rhamnosus CCFM1228.(2)The effects of Lactobacillus on gene transcription in hippocampus,prefrontal lobe,amygdala and hypothalamus of depressed mice were measured.Among them,L.paracasei CCFM1229 significantly up-regulated the transcription levels of Grin1,Grin2 a,Grin2b and other genes in depressed mice,which are of great significance to synaptic plasticity;L.paracasei CCFM1229 also significantly up-regulated the m RNA level of Mbp gene in depressed mice and maintained the stability of myelin structure and function of central nervous system(CNS);L.rhamnosus CCFM1228 significantly up-regulated the m RNA level of Gfap gene in prefrontal lobe of depressed mice and promoted the activation of astrocytes;In addition,CCFM1228 significantly inhibited the up-regulation of CD36 m RNA in hippocampus of depressed mice,so as to avoid depression like behavior caused by inflammatory corpuscle pathway.(3)After Lactobacillus intervention,the Chao1 index and observed species richness index of model mice increased significantly,and the Faith’s phylogenetic diversity index increased.However,there was no significant difference in Shannon index.β Diversity forms a new steady state.PICRUSt2 was used to predict the function of the gut microbiota.There were 139 different functional categories between the control group and the depression group.Some of the functional changes may be related to the modeling method and strength.After the intervention of Lactobacillus,some functions of the gut microbiota can be restored.(4)Compared with the model group,the intervention of 132M1,CCFM1229,8G3 and CCFM1228 decreased the activity of xanthine oxidase in cerebral cortex.CCFM1229 and CCFM1228 significantly increased the activity of adenosine deaminase in liver.(5)At the genus level,Anaerotruncus,Lachnospiraceae UCG-001,[Eubacterium]Coprostanoligenes Group,Ruminococcaceae UCG-005,Rikenellaceae RC9 gut group,Bifidobacterium,Coriobacteriaceae UCG-002,and Faecalibaculum were significantly negatively correlated with xanthine oxidase activity in cerebral cortex.Marvinbryantia was positively correlated with xanthine oxidase activity in cerebral cortex.All the above genera are related to depression related index,indicating that there is a close relationship between xanthine oxidase activity in cerebral cortex and depression phenotype mediated by gut microbiota.In conclusion,the intervention of L.paracasei 126L6,L.paracasei CCFM1229 and L.rhamnosus CCFM1228 reduced the anxiety and depression related behaviors of mice caused by chronic stress.The alleviating effect of CCFM1229 and CCFM1228 might be achieved by regulating the activity of brain xanthine oxidase,while the alleviating effect of L.paracasei126L6 on depression did not depend on the regulation of brain xanthine oxidase activity,and there might be other regulatory pathways.