腹泻型肠易激综合征与溃疡性结肠炎患者肠道菌群的关联分析

Comparative analysis of gut microbiota between ulcerative colitis patients and irritable bowel syndrome with predominant diarrhea patients

目的通过比较腹泻型肠易激综合征(IBS-D)与溃疡性结肠炎(UC)患者的肠道菌群特征,探索两者的关联。方法选择2020年5月至2021年12月在广州市第一人民医院消化内科住院的IBS-D和UC患者各24例,以及6名健康志愿者,收集新鲜人类粪便标本,提取DNA并进行16S rDNA高通量测序,对患者肠道菌群的多样性、优势菌群等进行统计学比较分析。结果代表菌群丰富度和均匀度的α多样性分析中,IBS-D组和UC组的Sobs指数、Chao1指数、ACE指数、goods_coverage指数、Shannon指数和Simpson指数分别为570.79±81.78 vs.566.50±84.30(P=0.859)、765.35±101.32 vs.749.15±90.53(P=0.562)、795.29±103.76 vs.781.81±94.02(P=0.639)、1.00±0.00 vs.1.00±0.00(P=0.261)、4.12±0.54 vs.4.07±0.50(P=0.730)、0.85±0.08 vs.0.85±0.07(P=0.904)。在Anosim检验(R=0.252,P=0.001)显示各组菌群组成存在一定差异的前提下,PCoA(PCO1+PCO2=40.11%)和NMDS(Stress=0.164)分析显示IBS-D和UC患者的肠道菌群结构偏离健康对照组但非常相近。IBS-D组和UC组实际检测的OTU数量分别为585和622,其中共有数量高达386;分别于门、科和属水平上对两组平均相对丰度排名前十的优势菌群进行比较,仅Acidobacteria(t=2.289,P=0.028)、Lachnospiraceae(t=2.036,P=0.049)、Peptostreptococcaceae(t=2.085,P=0.043)、Blautia(t=2.219,P=0.033)和Romboutsia(t=3.542,P=0.002)的差异具有统计学意义。与健康对照组相比,IBS-D组和UC组的Bifidobacterium和Enterococcus的平均相对丰度均有上调;Faecalibacterium、Prevotella-9和Anaerostipes的平均相对丰度均有下调;IBS-D组与UC组相比,UC组的Blautia平均相对丰度更高,IBS-D组的Romboutsia平均相对丰度更高。结论IBS-D和UC患者的肠道菌群丰富度、均匀度和结构高度相似,且“共享”大部分优势菌群。Enterococcus和Faecalibacterium丰度的改变可能介导了IBS-D和UC患者的腹泻症状,Blautia和Romboutsia丰度的差异可能与两种疾病腹泻性质不同相关。

Objective To explore the link between irritable bowel syndrome with predominant diarrhea(IBS-D)and ulcerative colitis(UC)through the analysis of the patient′s gut microbiota.Methods From May 2020 to December 2021,24 patients with IBS-D,24 patients with UC treated at Guangzhou First People′s Hospital and 6 volunteers were enrolled.All fresh stool specimens were collected and DNA were extracted for 16S rDNA high-throughput sequencing.α-diversity,β-diversity,and characteristic species were statistically analyzed and compared in phylum,family,and genus levels respectively.Results Inα-diversity analysis,which represented the richness of gut microbiota,the Sobs index,Chao1 index,ACE index,goods_coverage index,Shannon index and Simpson index of IBS-D group and UC group were 570.79±81.78 vs.566.50±84.30(P=0.859),765.35±101.32 vs.749.15±90.53(P=0.562),795.29±103.76 vs.781.81±94.02(P=0.639),1.00±0.00 vs.1.00±0.00(P=0.261),4.12±0.54 vs.4.07±0.50(P=0.730),0.85±0.08 vs.0.85±0.07(P=0.904).The microbial structure were approximate through PCoA(PCO1+PCO2=40.11%)and NMDS(Stress=0.164)analysis,while Anosim test(R=0.252,P=0.001)has showed significant difference.Numbers of actual detected OUTs are close(585 vs.622),of which the same OTUs are as high as 386.To compare the relative abundance of top ten species in phylum,family and genus level,only Acidobacteria(t=2.289,P=0.028),Lachnospiraceae(t=2.036,P=0.049),Peptostreptococcaceae(t=2.085,P=0.043),Blautia(t=2.219,P=0.033)and Romboutsia(t=3.542,P=0.002)had statistically significant differences.Compared to HC,the mean relative abundance of Bifidobacterium and Enterococcus was increased in both IBS-D and UC groups,while Faecalibacterium,Prevotella-9 and Anaerostipes was decreased.Conclusion Gut microbiota of IBS-D and UC are highly similar in richness,uniformity and structure.IBS-D and UC share most of the dominant microbiota.Among them,changes in the relative abundance of Enterococcus and Faecalbacterium may mediate diarrheal symptoms in IBS-D and UC patients.The reason why diarrhea in UC and IBS-D are different may come from Blautia and Romboutia.