原发性胆汁性胆管炎患者肠道菌群丰度及多样性与熊去氧胆酸短期应答的相关性

The relationship between ursodeoxycholic acid’s short-term response and abundance of intestinal flora and the diversity in patients with primary biliary cholangitis

目的 分析原发性胆汁性胆管炎(PBC)患者肠道菌群丰度及多样性与熊去氧胆酸(UDCA)短期应答的相关性。方法 选择苏州高新区人民医院2015年5月至2021年5月收治的86例PBC患者作为研究对象(研究组),另选取本院同期体检患者86例作为对照(对照组),比较PBC患者治疗前及治疗1个月后的各项血清生化指标水平;对比研究组治疗前及治疗1个月后丰度及多样性水平与对照组的差异;评估2组患者治疗1个月后UDCA短期应答情况并分析PBC患者丰度及多样性水平与UDCA短期应答的相关性;并评估治疗前PBC患者丰度及多样性水平对UDCA短期应答的预测价值。结果 PBC患者治疗1个月后血TBA、ALT、AST、TBil、WBC及Scr水平分别为(16.71±8.29)μmol/L、(27.49±10.25)U/L、(38.52±19.27)U/L、(18.54±7.31)μmol/L、(7.35±1.42)10;/L、(86.31±12.43)μmol/L,均低于治疗前[(32.27±11.45)μmol/L、(84.37±21.93)U/L、(88.37±31.62)U/L、(27.38±8.12)μmol/L、(14.52±2.17)×10;/L、(148.59±23.16)μmol/L],差异均具有统计学意义(P<0.05);治疗前,研究组丰度(Chao1指数)及多样性水平(Shannon指数)分别为441.59±35.49、2.54±0.68,均低于对照组(706.35±42.17、3.31±0.46),差异有统计学意义(P<0.05);治疗1个月后,研究组Chao1指数及Shannon指数较治疗前均升高,差异有统计学意义(P<0.05);治疗1个月后,研究组Chao1指数及Shannon指数分别为631.27±51.36、3.01±0.59,均低于对照组(703.49±42.76、3.37±0.53),差异有统计学意义(P<0.05);Spearman相关性分析结果显示,患者丰度水平(r=0.772,P=0.024)、多样性水平(r=0.683,P=0.037)均与UDCA短期应答呈正相关;ROC分析显示,丰度及多样性对PBC患者UDCA短期应答的ROC预测的灵敏度分别为74.14%、72.41%,特异度分别为60.71%、64.29%,曲线下面积(AUC)分别为0.764、0.737。结论 PBC患者肠道菌群丰度及多样性均与UDCA短期应答呈正相关,且丰度及多样性水平对PBC患者UDCA短期应答具有一定的临床预测效能。

Objective To analyze the correlation between the abundance and diversity of intestinal flora in patients with primary biliary cholangitis(PBC)and the short-term response of ursodeoxycholic acid(UDCA).Methods 86 patients with PBC admitted to our hospital from May 2015 to May 2021 were selected as the research object(research group),and86 patients with physical examination at the same time in our hospital were selected as the control(control group).We compared serum biochemical index levels of PBC patients before and one month after treatment.We also compared the differences in abundance and diversity between the research group before and one month after treatment with the control group.Then we evaluated the short-term response of UDCA in the two groups after one month of treatment and analyzed the correlation between the abundance and diversity of PBC patients and the short-term response of UDCA.The predictive value of the abundance and diversity of PBC patients before treatment on the short-term response of UDCA was assessed.Results The levels of TBA,ALT,AST,TBil,WBC and Scr in PBC patients after 1 month of treatment were(16.71 ±8.29)μmol/L,(27.49± 10.25)U/L,(38.52 ± 19.27)U/L,(18.54 ± 7.31)μmol/L,(7.35 ± 1.42)×10;/L,(86.31± 12.43)μmol/L,which were all lower than those before treatment[(32.27 ± 11.45)μmol/L,(84.37 ±21.93)U/L,(88.37± 31.62)U/L,(27.38±8.12)μmol/L,(14.52±2.17)×10;/L,(148.59±23.16)μmol/L],the differences were statistically significant(P<0.05).Before treatment,the abundance(Chao1 index)and diversity level(Shannon index)of the research group were(441.59± 35.49)and(2.54± 0.68),respectively,which were lower than those of the control group(706.35± 42.17,3.31 ± 0.46),and the difference was statistically significant(P<0.05).After 1 month of treatment,the Chao1 index and Shannon index of the research group were higher than those before treatment,and the difference was statistically significant(P<0.05).And after 1 month of treatment,the Chao1 index and Shannon index of the research group were(631.27±51.36),(3.01±0.59)respectively,were all lower than those in the control group(703.49 ± 42.76),(3.37 ± 0.53),the difference was statistically significant(P<0.05).Spearman correlation analysis showed that the abundance level(r=0.772,P=0.024),diversity level(r=0.683,P=0.037)were positively correlated with short-term UDCA response.ROC analysis showed that the sensitivity of abundance and diversity to ROC prediction of short-term UDCA response in PBC patients were 74.14%,72.41%,respectively,the specificity were 60.71%,64.29%,and the area under the curve(AUC)were 0.764 and 0.737,respectively.Conclusion The abundance and diversity of the intestinal flora of PBC patients are positively correlated with the short-term UDCA response,and the abundance and diversity level have a certain clinical predictive power for the short-term UDCA response of PBC patients.