胆汁淤积性肝病患者肠道真菌多样性及构成改变

Changes in intestinal fungal diversity and compositions in patients with cholestatic liver disease

目的分析胆汁淤积性肝病患者和健康对照人群的肠道真菌菌群多样性及构成改变。方法收集胆汁淤积性肝病患者(n=20)和健康人群对照者(n=22)的新鲜粪便,采用ITS2 DNA测序测定肠道真菌,运用生物信息学方法分析两组间真菌菌群多样性、结构、功能特征之间的差异,以及肠道真菌与临床参数间的相关性。结果两组年龄、性别构成、吸烟等均无统计学差异(P>0.05)。胆汁淤积性肝病患者组与健康人群对照组相比血清学指标均显著升高(P<0.05);两组间肠道真菌Alpha多样性无显著差异(P>0.05);Beta多样性有显著差异(P<0.01);胆汁淤积性肝病患者组Myceliophthora相对丰度增加(P<0.01),Diutina相对丰度降低(P<0.01);LEfSe分析结果表明胆汁淤积性肝病患者组中Myceliophthora显著富集,且腐生-共生(Saprotroph-Symbiotroph)菌的丰度显著低于健康人群对照组(P<0.05);Spearman相关系数分析结果显示Myceliophthora与ALT(P<0.05)、AST、ALP、GGT、TBIL、DBIL(P<0.01)均呈正相关。结论胆汁淤积性肝病患者与健康人群相比肠道真菌菌群构成有特征性改变,Myceliophthora与胆汁淤积性肝病患者疾病严重程度密切相关。

Objective To analyze the changes in intestinal fungi and compositions in patients with cholestatic liver disease from healthy individuals.Methods Fresh feces from 20 patients with cholestatic liver disease and 22 healthy individuals were collected.The intestinal fungi were determined by ITS2 DNA sequencing,and the differences of fungal flora diversity,structure and functional characteristics between the 2 groups were analyzed by bioinformatics methods,and the correlation between intestinal fungi and clinical parameters was analyzed.Results There were no significant differences in age,sex composition and smoking between the 2 groups(P>0.05).The serological indexes were significantly higher in the patients with cholestatic liver disease than the healthy controls(P<0.05).No significant difference was seen in the Alpha diversity of intestinal fungi between the 2 groups(P>0.05),but significant differences were observed in Beta diversity(P<0.01).The relative abundance of Myceliophthora was increased(P<0.01)and that of Diutina was decreased(P<0.01)in the patients with cholestatic liver disease.LEfSe analysis showed that Myceliophthora was significantly enriched in the patients,and the abundance of Saprotroph-Symbiotroph was significantly lower in the patients than the healthy controls.Spearman correlation coefficient analysis showed that Myceliophthora was positively correlated with alanine transaminase(ALT,P<0.05),and aspartate transaminase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase(GGT)and total bilirubin(TBIL)(P<0.01).Conclusion Characteristic changes are seen in intestinal fungal compositions between the patients with cholestatic liver disease and the healthy controls.Myceliophthora is closely associated with the severity of the disease.