| Research backgroundDepression is a serious mental illness that can have disastrous consequences for a person’s physical and mental health.However,standard drug treatment regimens,such as antidepressants,have limited efficacy and significant adverse reactions and resistance.Brain-gut-axis disorder caused by intestinal flora disorder has become the most popular mechanism of depression in recent years.Many studies have found that depression symptoms can be alleviated by restoring an imbalance in the gut flora of depressed patients.Fermented probiotic foods are emerging health therapies related to restoring intestinal disorders in patients with depression.Wheat germ is an inexpensive raw material that is rich in bioactive ingredients,aminobutyric acid of which has been shown to have antidepressant effects,and the results of several studies have shown that Lactobacillus plantarum has significant therapeutic effects in alleviating depression,and that it is the main GABA producing bacterium.FWG,which was obtained by Lactobacillus plantarum fermentation of wheat germ,is rich in probiotics,prebiotics,protein,short-chain fatty acids and GABA,which theoretically has the effect of alleviating depression.Based on the above reasons,this study speculated that wheat embryo fermentation has the potential to relieve depression by interfering with brain-gut axis.Research purposeBy establishing a rat model of chronic and unpredictable mild stress(CUMS),validating whether FWG can intervene nutritionally in a depression rat model and explore its potential mechanism of alleviating depression from the perspective of brain-gut axis.Research methodIn this study,firstly,single factor experiment and response surface experiment were used to optimize the process parameters of GABA production from wheat embryo by Lactobacillus plantaris fermentation(and characterize its structure).T Subsequently,the CUMS depressive rat model was constructed,and the changes of CUMS rats after the intervention of FWG were observed through behavioral experiments,physiological and biochemical tests and other experiments.Finally,high-throughput sequencing was used to investigate the changes in rat intestinal flora in the model group as well as the effects of wheat germ ferments on intestinal microecology in CUMS rats in order to better understand the potential mechanisms of FWG nutritional intervention in depression.Research results(1)Optimization of fermentation conditions for GABA production from wheat embryo by probiotic fermentation: The optimal conditions for GABA production from wheat embryo by probiotic fermentation were determined by single factor response surface experiment as inoculation amount =3.82%;p H=4.45;Fermentation time =24.8h.Fermentation degraded the macromolecular proteins in FWG and increased the content of free amino acids in wheat germ extract,which improved the degree of absorption and nutritional value of FWG.(2)Effects of wheat embryo fermentation on behavioral characteristics of depressed rats:FWG significantly improved the body mass index of CUMS rats,and there was no significant difference between high-dose FWG group and blank control group;FWG intervention significantly increased the number of open-arm dwellings(OE),open-arm dwell time(OT),and total number of entries into the open and closed arms(OE+OT)in CUMS rats in the elevated cross-maze experiment(EPM);FWG intervention significantly reduced immobility time in CUMS rats in the forced swimming experiment(FST).In open field test,FWG can significantly increase the total number of cells traversed,number of uprights and crossing the central grid by CUMS rats;In the Sucrose Preference Test(SPT),FWG was able to significantly increase the sucrose preference rate in CUMS rats.(3)Effects of wheat germ ferment on physiological and biochemical indexes in CUMS rats: To further investigate the basis of phenotypic validation of FWG intervention in depression,a CUMS model was established in SD rats to explore the effects of FWG on neurotransmitter indexes,blood lipid levels,liver function and hippocampal substructure changes in CUMS rats.The results showed that FWG could significantly increase the contents of 5HT,5HIAA,ACH and GABA in the hippocampus of CUMS rats(p<0.05);It can significantly reduce the TG and TC contents,GOT and GPT activities in the serum of CUMS rats(P < 0.05);Increasing the total antioxidant capacity in the serum of rats.(P <0.05);It also can reverse the symptoms of abnormal neuronal cell morphology and structure,significantly reduced cell number and disorganized arrangement in the DG,CA3 and CA1 hippocampal sub-structures of CUMS rats.(4)Effects of FWG on gut microbiota of CUMS rats: Firstly,the biodiversity of intestinal flora was analyzed.α-diversity analysis showed that FWG could significantly improve the Sobs index and Shannon index of intestinal flora in CUMS rats;β-diversity PCo A showed that there were significant differences between the intestinal flora of CUMS rats and healthy control rats,and the intestinal flora of FWG rats was similar to that of blank control rats;secondly,differential flora analysis was performed at two taxonomic levels,family and genus.FWG could significantly increase Peptostreptococcaceae,Lachnospiraceae,Oscillospiraceae,Romboutsia and intestinal flora in CUMS rats Unclassified＿f＿＿Lachnospiraceae bacteria such as abundance(P < 0.05),The abundance of Lactobacillaceae,Erysipelotrichaceae,Lactobacillus and Marvinbryantia was significantly decreased(P < 0.05).The strong correlation between neurotransmitters and gut microbiota was shown in the correlation analysis between gut flora and neurotransmitters,revealing an important role of gut flora in alleviating depression,as a result,it lends credence to the idea that brain-gut-axis abnormalities induce depression.In the end,the prediction of intestinal flora function showed that there was abnormal amino acid metabolism in CUMS rats and that FWG could restore the abnormal amino acid metabolism.Research conclusionIn this study,we demonstrated that FWG improved depression-like behavior in CUMS model rats and the symptoms of dyslipidemia decreased total antioxidant capacity and liver function injury were reversed in CUMS rats.FWG also increases levels of neurotransmitters in the hippocampus and restores damaged hippocampal substructures.In addition,our results on the effects of wheat germ fermentation on gut microbiota in CUMS rats provide support for the role of gut microbiota in brain health and the antidepressant effect of FWG on the gut microbiota-brain axis.Our results provide support for the role of gut microbiota in brain health and the antidepressant role of FWG in the gut microbiota-brain axis.In particular,FWG can effectively change the structure of intestinal flora in CUMS rats,reshape intestinal flora,restore neurotransmitter levels and amino acid metabolism in depressed rats through brain-enteric-axis.Taken together,we believe that FWG has antidepressant potential.The results of this study provide a new idea for the clinical treatment of depression,and also provide theoretical support for the development of new safe anti-depression functional food. |
PDF Full Text Request