Correlation Between Intestinal Flora And Activity Of Ulcerative Colitis

Background:Ulcerative colitis(UC)is a chronic nonspecific inflammatory bowel disease.In recent years,changes in intestinal flora have been found to be associated with the occurrence and progression of UC,which may determine its prognosis and disease progression.We previously found that metformin can slow down the colitis induced by sodium dextran sulfate(DSS)in mice,which may be related to its regulation of the species diversity and abundance of intestinal flora.It has been found in animal experiments that the occurrence and progression of colitis is closely related to changes in intestinal flora.Therefore,we want to further verify whether changes in intestinal flora are related to disease activity in UC patients.Aim:To study the change characteristics of intestinal flora diversity under different inflammatory activities in UC patients;To explore whether the different characteri-stics of gut microbiota in active and remission stages of UC can be used as a means of predicting disease recurrence and potential therapeutic targets.Methods:To collect stool samples from 9 patients with incipient or chronic relapsing active UC who met the diagnostic criteria for UC and who reached remission after treatment;plus stool samples of 9 normal controls without intestinal lesions.Using DNA extraction,PCR amplification,Illumina Miseq sequencing and data processing were used to obtain data results,and the diversity analysis,intestinal flora composition and difference analysis,and Lef Se analysis were used to screen key differential bacterial genera before and after UC treatment and compare the composition and structure of the intestinal flora between the same group of patients and the normal group before and after treatment.Results:1.A total of 18 subjects were included in this study,including 9 UC patients and 9 normal people.There were 8 males and 1 female in the UC group,aged 39±15years,and 5 males and 4 females in the normal group,aged 28±7 years.The baseline data of the UC group and the normal group were balanced.2.The laboratory index results of UC patients before and after treatment showed that compared with before treatment,calprotectin,complement C3,hs-CRP,ESR,PLT,and PCT decreased significantly after treatment(P<0.05);Hb,ALB,MCV,HCT It was significantly higher than that before treatment(P<0.05).3.Comparison of the α diversity of intestinal flora in UC patients before and after treatment with normal people: The dilution curve showed that all samples reached a plateau,indicating that the sequencing results were sufficient to reflect the diversity of the intestinal flora of the samples.The abundance and diversity of flora in UC patients were significantly lower than those in normal people(P<0.05);the abundance and diversity of intestinal flora in UC patients after treatment showed an upward trend compared with those before treatment.4.Comparison of the β diversity of intestinal flora in UC patients before and after treatment and in normal people: The intestinal flora structure of UC patients was significantly separated from that of normal people(Adonistest P<0.01),suggesting that the intestinal flora structure of UC patients was significantly different from that of normal people.Moreover,the distance between the samples after treatment and the samples from normal people was closer,indicating that the structure of intestinal flora after UC treatment was closer to that of normal people than before treatment.5.Analysis of differences in species composition of all samples: At the phylum level,the intestinal flora is mainly composed of Firmicutes,Actinobacteria,Proteobacteria,Bacteroidota and Fusobacteriota consists of 5 categories,Firmicutes and Bacteroidetes in normal people accounted for more than 90% of the community.The predominant phylum in the intestine of normal people is Firmicutes,and the predominant phyla in UC group are Actinobacteria and Proteobacteria,Bacteroidota showed little difference between normal and UC groups;The dominant bacterial genera in the gut were Faecalibacterium,Blautia,Subdoligranulum,and Fusicatenibacter,and the dominant bacterial genera in the UC group were Escherichia-Shigella,Ruminoco-ccus＿gnavus＿group,and Veillonella.Before UC treatment,Ruminococcus＿gnavus＿group and Lactobacillus were significantly increased(P<0.05).However,Agathobacter,Roseburia and Subdoligranulum were significantly lower than normal subjects(P<0.01).In the UC group,there were significant decreases in Rothia and Granulicatella after treatment compared with those before treatment(Wilcoxon P< 0.05).6.Lefse analysis to screen for differential bacterial genera: The differences in gut microbiota at the phylum,class,order,family,and genus levels were compared between the pre-UC group and normal individuals,and a total of 95 species with significant differences between the groups were screened.The relative abundance of79 bacterial groups in normal people was higher than that before UC treatment(P<0.05): f＿＿Ruminococc,g＿＿Roseburia,f＿＿Prevotellaceae,etc.The relative abundance of 16 bacterial groups before UC treatment was higher than that of normal people(P<0.05),namely: g＿＿Ruminococcus＿gnavus＿group,o＿＿Enterobact-erales,f＿＿Enterobacteri-aceae,etc.The differences in gut microbiota at the phylum,class,order,family and genus levels before and after treatment in the UC group were compared,and a total of 4 species with significant differences were screened out.The relative abundance of 3 microorganis-ms before treatment was higher than that after treatment: g＿＿Rothia,f＿＿Carnobacteriaceae,g＿＿Granulic-atella,while after treatment,the relative abundance of o＿＿Peptostreptococcales-Tissierellales was higher.The relative abundance was higher than before treatment.Conclusion:1.The abundance and diversity of intestinal flora in UC patients were significantly lower than those of normal people,mainly reflected in the reduction of beneficial bacteria and the increase of opportunistic pathogenic bacteria.2.There are significant differences in the composition and structure of intestinal flora in UC patients compared with normal people.However,the imbalance of intestinal flora in patients in remission was partially restored after treatment.3.The decrease of various inflammatory indexes in UC patients after treatment may be related to the correction of the imbalance of intestinal flora,suggesting that maintaining the balance of intestinal flora may be a potential therapeutic target for reducing disease recurrence.