Investigation On The Mechanism Of Yeast β-glucan On COPD By Multi-omics Analysis

At present,the number of chronic obstructive pulmonary disease(COPD)patients in China is 99,000,000,which has become a chronic disease equate to hypertension and diabetes,and constitutes a major burden of disease.Yeast β-glucan has significant biological activities such as immunoregulation,metabolism regulation,anti infection,anti radiation and so on.It has a certain effect in the protection of lung injury.However,the efficacy evaluation and mechanism of its intervention in COPD are still insufficient.Considering the huge population health needs and the increasing national medical burden caused by chronic pulmonary obstruction,and the basis of the potential effect of yeast β-glucan in the intervention of chronic pulmonary obstruction,the anti-pulmonary effect of yeast β-glucan was studied systematically.First,the model was made by smoking and lipopolysaccharide to simulate the chronic pulmonary obstruction caused by smoking or PM2.5.The intervention effect and mechanism of yeast β-glucan was studied in SD rats on chronic obstructive lung.Secondly," Lung and large intestine have relevance ",the changes of pulmonary flora and intestinal flora are strongly related to the slow obstructive lung.This study explores the changes of pulmonary flora and intestinal flora in rats with chronic pulmonary obstruction and the effect of yeast β-glucan on the flora.Finally,The effect of yeast β-glucan on the expression of protein and metabolites in lung tissue of rats with chronic obstructive pulmonary disease;At the same time,the slow obstruction of lung may affect the oxygen supply and blood supply to the brain,even lead to pulmonary encephalopathy,affect the brain tissue and change the protein expression.In this paper,we try to find the relationship between the two.Through bioinformatics analysis,the relationship between lung gut(Flora)and brain was explored to reveal yeast β-glucans may act on mechanisms to fill gaps in understanding in this area.The main results of this study are as follows:1.The COPD rat model was established by the combination of smoking and lipopolysaccharide.The SD rats were used as experimental animals.The pathological observation,lung function test,lung lavage fluid and intestinal immune cells / factors level,SOD level and other multi-dimensional evaluation were used to evaluate the effect of yeast β-Glucan has on anti-COPD.Yeast β-glucan can improve lung compliance,tidal volume,lung function,inflammatory factors and SOD oxidative stress.To some extent,yeast β-glucan can reduce the damage of bronchial tissue,reduce the number of pulmonary bullae and improve the inflammation of bronchial wall.2.Effects of yeast β-glucan on pulmonary and intestinal flora in COPD rats by microbiome was investigated.Yeast β-glucan had significant effects on the diversity and evenness of pulmonary flora in COPD rats.Yeast β-glucan significantly increased the abundances of Firmicutes,Bifidobacterium pseudolongum and Bifidobacterium animalis,and decreased the abundances of actinomycetes,Clostridium,bifidobacteriaceae and powdery mildew.Effects of yeast β-glucan on the composition and abundance of intestinal flora in COPD rats.Yeast β-glucan significantly increased Firmicutes,lactobacilliaceae,Bifidobacterium pseudolongum,Bifidobacterium animalis,decreased Actinobacteria,bifidobacilliaceae,Myristicaceae,powdery mildew,and identified 17 marker species,including lactobacilli,lactobacilli,lactobacilliaceae.The predominant bacteria in the lung and intestinal flora of COPD rats were similar,and they were mainly Firmicutes and lactobacilli.There were some similarities in the composition and abundance changes of pulmonary and intestinal flora after yeast β-glucans intervention in model rats.At the phylum level,the effect on the distribution of pulmonary and intestinal flora was the same,which significantly increased the proportion of firmicum and decreased the proportion of actinomycetes.At the family level,the proportion of bifidobacteriaceae and powdery mildew was significantly decreased.In addition,the proportion of Clostridium was significantly decreased in the pulmonary flora,and the proportion of Lactobacillus and nutmeg was significantly increased in the intestinal flora.At the genus level,the proportions of Bifidobacterium pseudolongum and Bifidobacterium animalis were significantly increased.3.Effects of yeast β-Glucan by proteome on protein expression in lung and brain tissue of COPD rats was studied.Yeast β-glucan can affect the protein expression in lung tissue,which is mainly manifested in the significant changes of adrenergic signaling in myocardial cells,nonalcoholic fatty liver disease,VEGF signaling pathway,focal adhesion and central carbon metabolism in cancer.Among them,raf1,adcy5,gnai1 and CALM1 were expressed in multiple pathways.The analysis of protein-protein interaction network showed that the core associated proteins were c4 bpa,FGB,FGG,ZPI,C3,FGA and raf1.We found four immune system related pathways: complement and coagulation cascade,platelet activation,FC ε RI signaling pathway and AMPK signaling pathway suggest that immune regulation is an important pathway for anti COPD.Yeast β-glucan affects protein expression in brain tissue,mainly in complement and coagulation cascade,platelet activation,oxytocin signaling pathway,Gn RH signaling pathway,melanogenesis,neurotrophin signaling pathway and other important pathways.AKT2,pik3 cb,mapk1 and map2k1 were expressed in many pathways.The core associated protein was FGA.The difference of protein expression between lung and brain tissues was found in yeastβ-glucan has significant changes in Rap1 signaling pathway,amino sugar and nucleotide sugar metabolism,leukocyte trans endothelial migration,platelet activation,systemic lupus erythematosus pertussis and other important pathways.The analysis of differentially expressed protein-protein interaction network showed that the core associated protein was FGA,which may be one of the important regulatory targets.The differential protein expression of lung brain tissue showed a certain correlation in leukocyte trans endothelial migration,platelet activation,systemic lupus erythematosus and Rap1 signaling pathway.4.Thirty significant metabolites,including trimethylamine N-oxide,DL indole-3-lactate,were obtained by identification of the metabolites of blood.The abundant metabolites in protein digestion and absorption,pyrimidine metabolism,amino acid biosynthesis,bile secretion and tryptophan metabolism were more significant.Among them,L-glutamine,L-tryptophan,o-aminobenzoic acid(vitamin L1),2-oxo-octanoic acid and tyramine are involved in multiple metabolic pathways.L-Glutamine metabolism produces glutathione and NADPH,which can reduce oxidative stress,and maybe it is also yeast β-Glucan interferes with a pathway in the slow lung obstruction.Tryptophan metabolism is closely related to central nervous system diseases,inflammation,immunity,etc.,which is closely related to the anti slow lung obstruction.5.Comprehensive analysis shows that The prognosis of yeast β-glucan affects the protein expression,metabolic products and other important pathways,the composition and changes of the lung and intestinal flora,which are closely related to the important factors of the development of slow obstructive lung,such as inflammation,autonomic nervous system dysfunction,increased cholinergic nervous tension,oxidative stress,immunity,etc.Among them,tryptophan metabolism pathway,VEGF signal pathway,adrenergic signal in cardiac cells,neurotrophin signaling pathway,local adhesion and bacterial group changes are closely related to chronic obstructive lung.After further verification,the possible mechanism network diagram is sorted out.