摘要
目的分析高原地区慢性肝病患者肠道菌群物种多样性及菌群丰度结构变化,探讨肠道微生态失衡与慢性肝病的关联。方法收集高原地区90例慢性肝病(慢性乙型病毒性肝炎30例、乙肝后肝硬化30例、原发性肝癌30例)及25例健康人的粪便,利用高通量基因测序及生物信息学分析技术,探讨慢性肝病患者与健康人之间物种多样性以及不同分类水平上肠道菌群组成是否存在差异。结果慢性肝病患者肠道菌群多样性较健康人显著降低(Z=1.462,P=0.005),Beta多样性分析发现慢性肝病患者与健康人肠道菌群组成上差异存在统计学意义(r=0.122,P=0.020);对慢性肝病组与健康组进行组间肠道菌群差异性分析,发现在门水平上,拟杆菌门在慢性肝病组中富集(Z=1.065,P=0.043),慢性肝病组内比较发现拟杆菌门在慢性乙型病毒性肝炎、乙肝后肝硬化、原发性肝癌患者中的相对丰度呈逐渐减少的趋势,但差异无统计学意义(P>0.050);属水平上,粪杆菌属在慢性肝病组中富集(Z=1.092,P=0.032),而肠球菌属分布减少(Z=1.398,P=0.036),同时慢性肝病患者肠道菌群中一些潜在致病菌如链球菌属、韦荣球菌属较健康人富集,而双歧杆菌属、乳杆菌属等益生菌相对丰度较低,但差异无统计学意义。组内比较发现存在差异菌属链球菌属(H=6.026,P=0.049)、韦荣球菌属(H=10.317,P=0.005),对差异菌属进行两两比较发现相较原发性肝癌组,链球菌属在乙肝后肝硬化组中更加富集,差异有统计学意义(P<0.050),同时发现肝硬化及肝癌组中韦荣球菌属的相对丰度较慢性乙型病毒性肝炎组高,但差异无统计学意义(P>0.050)。相关性分析发现粪杆菌属与ALT、AST、ALP水平呈正相关(r=0.192、0.187、0.276,均P<0.050),韦荣球菌属与TB、ALP水平呈正相关(r=0.257、0.225,均P<0.050)。结论高原地区慢性肝病患者肠道微生物多样性显著降低,且慢性肝病患者与健康人肠道菌群组成上存在差异,在慢性肝病的进展中一些潜在致病菌的丰度逐渐增加,同时益生菌的相对丰度呈逐渐减少的趋势。
Objective To investigate the species diversity and abundance structure of intestinal flora in patients with chronic liver disease(CLD)at high altitude regions.Methods Fecal specimens were collected from 90 cases of chronic liver disease(30 cases of chronic hepatitis B,30 cases of hepatitis B cirrhosis,30 cases of primary liver cancer)and 25 healthy individuals in plateau area.High-throughput gene sequencing and bioinformatics analysis were used to explore the differences in species diversity and composition of intestinal flora between the patients and healthy controls.Results The diversity of intestinal flora in patients with CLD was significantly lower than that in healthy controls(Z-1.462,P-=0.005).Beta diversity analysis showed that there were differences in the composition of intestinal flora between patients with CLD and healthy controls(r=0.122,P=0.020).At phylum level,Bacteroidetes enriched in CLD group(Z=1.065,P=0.043);its relative abundances in chronic hepatitis B,hepatitis B cirrhosis and primary liver cancer showed a trend of gradual de-crease,but the differences were not statistically significant(P>0.050).At the genus level,Faecalibacterium was enriched in the chronic liver disease group(Z-1.092,P=0.032),while Enterococcus was decreased(Z-1.398,P=0.036).At the same time,some potential pathogenic bacteria such as Streptococcus and Veillonella were enriched in the intestinal flora of patients with chronic liver disease,while the relative abundance of probiotics such as Bifidobacterium and Lactobacillus was low,but the difference was not statistically significant.There were different bacteria in the group,Streptococcus(H=6.026,P=0.049)and Veillonella(H=10.317,P-0.005).Compared with the primary liver cancer group,Streptococcus was more enriched in the hepatitis B cirrhosis group,and the difference was statistically significant(P<0.050);At the same time,we found that the relative abundance of Vellonella in liver cirrhosis and liver cancer group was higher than that in chronic hepatitis B group,but the difference was not statistically significant(P>0.050).The correlation analysis showed that Faecalibacterium was positively correlated with ALT,AST and ALP(r=0.192,r=0.187,r=0.276,all P<0.050),and Veillonella was positively correlated with TB and ALP(r=0.257,r=0.225,all P<0.050).Conclusion The intestinal microbial diversity of patients with CLD in plateau area decreased significantly,and there are differences in the composition of intestinal flora between the patients and healthy individuals.In the progression of CLD,the abundance of some potential pathogenic bacteria gradually increased,and the relative abundance of probiotics gradually decreased.
作者
张宏琳
王学红
李焱
陶嘉楠
ZHANG Hong-lin;WANG Xue-hong;LI Yan;TAO Jia-nan(Graduate School of Qinghai University,Xining,Qinghai 810016,China;不详)
出处
《中国微生态学杂志》
CAS
CSCD
2022年第9期1018-1023,共6页
Chinese Journal of Microecology
基金
青海省消化系统疾病临床医学研究中心项目(2019-SF-L3)。
关键词
慢性肝病
肠道微生态
物种多样性
结构变化
Chronic liver disease
Intestinal microecology
Species diversity
Structural changes
