| Objective: To observe the clinical effect of Liujunzi decoction on chronic persistent asthma patients of lung spleen qi deficiency syndrome and its influence on gut and respiratory microbiota.At meanwhile,the correlation between gut and respiratory microbiota and clinical indicators were also analyzed so as to clarify the possible mechanism of "paracme with strengthening earth to generate metal" method in the treatment of asthma by correlation analysis.Method:1.Seventy-two chronic persistent asthma patients of lung spleen qi deficiency syndrome were selected and randomly divided into the treatment group and control group,with 36 cases in each group.The control group was treated with inhaled glucocorticoid and long-acting ?2 receptor agonist(ICS/LABA)as-need,while the treatment group was treated with Liujunzi Decoction(1 bag each time,twice a day)on the basis of ICS/LABA.The patients in both groups were treated for 4 weeks and followed up for 12 weeks.The changes of ACT score,TCM symptom score,lung function index,Fe NO score and eosinophil proportion were observed before and after treatment a nd during follow-up,and the acute exacerbation risk and ICS usage were compared between the two groups.2.In the treatment group and control group,10 patients were randomly selected as the research object,and 10 healthy volunteers were also selected as the negative control.Fecal and induced sputum samples were collected before and after treatment by disposable sample collection box.Genomic DNA of fecal and sputum samples were extracted,and then high-throughput sequencing of Illumina Miseq was performed,and biological information was analyzed to study the differences in gut and respiratory microbiota among these groups.3.Clinical data of patients in the above groups and healthy control group were collected,and the correlation between gut and respiratory microbiota and asthma condition were analyzed by Pearson correlation analysis;further the similarity between gut and respiratory microbiota,and the correlation with clinical indicators of patients after treatment were also analyzed.Results:1.A total of 32 patients in the treatment group and 31 patients in the control group were included in the data analysis.ACT score increased significantly post-treatment,follow-up 1,follow-up 2,follow-up 3 in the treatment group when compared with pre-treatment,while TCM symptom score decreased significantly,the differences were statistically significant(P<0.01)and the treatment group was significantly better than the control group,the differences were statistically significant(P<0.01).Compared with pretreatment,FEV1% Pred,PEF and FEV1/FVC in the treatment group were significantly increased,Fe NO score and eosinophil ratio were significantly decreased,the differences were statistically significant(P<0.01)and the treatment group was significantly better than the control group,the differences were statistically significant(P<0.01).During the treatment period,there was no withdrawal from the treatment due to acute exacerbation of asthma in both groups.One case in the treatment group had chest tightness and shortness of breath,while six cases in the control group had wheezing and shortness of breath.The risk of acute exacerbation in the treatment group was better than that in the control group(P=0.042).The total usage of ICS in the treatment group was significantly lower than that in the control group(P<0.01).2.In terms of species richness,Ace and Chao1 index showed that the gut microbiota richness of asthmatic patients was significantly lower than that of healthy control group,while respiratory microbiota richness of asthmatic patients was significantly higher than that of healthy control group.I n terms of species diversity,the Shannon index of gut microbiota in asthmatic patients was significantly lower than that of healthy control group,and the Simpson index was significantly increased,while the Shannon index of respiratory microbiota in asthmatic patients was significantly higher than that of healthy control group,and the Simpson index was significantly decreased,differences between the two groups were statistically significant(P<0.01).In the analysis of species difference between the two groups,the abundance of gut and respiratory microflora in asthmatic group and healthy control group changed significantly from phylum to genus level;Lef Se analysis showed that F i r mi cu t es and A ct i n o myc et a l es were increased in gut and respiratory of healthy control group,while Proteobacteria was increased in gut and respiratory of asthmatic group.Compared with pre-treatment,Ace,Chao1 and Shannon index of gut microbiota were significantly increased,Simpson index decreased significantly after Liujunzi decoction treatment,while Ace,Chao1 and Shannon index of respiratory microbiota were significantly decreased,Simpson index increased significantly after Liujunzi decoction treatment(P<0.01 and P<0.05).Ace,Chao1,Shannon and Simpson index of gut microbiota in the control group did not change after treatment(P>0.05).After treatment,the Shannon index of respiratory microbiota in the control group was significantly decreased,while the Simpson index was significantly increased,and the differences were statistically significant(P<0.01 and P<0.05),while there were no significant effect on Ace and Chao1 index in respiratory microbiota,and the differences were not statistically significant(P>0.05).And Ace,Chao1 and Shannon index of Liujunzi group were significantly lower than those of placebo group,while Simpson index was significantly higher than that of placebo group in post-treatment period(P<0.01 and P<0.05).After treatment,the Ace,Chao1 and Shannon indexes of gut microbiota in the treatment group were significantly higher than those in the control group,and the Simpson index was significantly lower than that in the control group,while the Ace,Chao1 and Shannon indexes of respiratory microbiota in the treatment group were significantly lower than those in the control group,and the Simpson index was significantly higher than that in the control group,and the differences were statistically significant(P<0.01 and P<0.05).In the analysis of species difference between the two groups,the abundance of gut and respiratory microbiota in the two groups before and after treatment had significant changes from phylum to genus level;Lef Se analysis showed that Firmicutes and Bacteroidales were increased in the gut and respiratory microbiota in the treatment group,while Allobaculum and F u s o b a ct er i a were mainly increased in the gut and respiratory microbiota of the control group.3.The abundance of gut and respiratory microbiota in asthmatic patients was significantly correlated with the history of asthma and number of asthma hospitalizations per year.By crossing the different gut and respiratory microbiota,16 kinds of genus were obtained,which including Paraprevotella,Alistipes,Adlercreutzia,Pseudomonas,Olsenella,Gemmiger,Klebsiella,Oscillibacter,Odoribacter,Prevotella,Neisseria,Bifidobacterium,V ei l l o n el l a,L a ct o b a ci l l u s,R o s eb u r i a,a n d P a r a b a ct er o i d es.T h e r es u l t s o f co rr el at i o n an al y s i s s h o w ed t h at t h e ab u n d an ce o f t h es e b a ct eri a was s i g n i fi can t l y c o rr el a t ed wi t h l u n g fu n ct i o n i n d ex,AC T s c o re,eo s i n o p h i l p erc en t ag e,T C M s y m p t o m s co re an d Fe NO o f as t h m a.Conclusions:1.Liujunzi decoction can improve the clinical symptoms and lung function of chronic persistent asthma patients of lung spleen qi deficiency syndrome,reduce the risk of re acute exacerbation and usage of ICS.2.The gut and respiratory microbiota of asthmatic patients changed significantly.Liujunzi decoction can regulate the richness and diversity of gut and respiratory microbiota of asthmatic patients,and restore the gut and respiratory microbiota homeostasis.3.There is a significant correlation between gut and respiratory microbiota.Liujunzi decoction treat asthma by regulating the gut microbiota and then restoring the steady state of respiratory microbiota. |
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