逍遥丸对肝郁脾虚证自身免疫性肝炎患者肠道菌群的干预作用

Xiaoyao Pill alters gut microbiota of autoimmune hepatitis patients with liver depression and spleen deficiency syndrome

目的 基于“肠肝轴”探讨逍遥丸对肝郁脾虚证自身免疫性肝炎(AIH)患者肠道菌群的干预作用。方法 共纳入60例在浙江中医药大学附属杭州市西溪医院确诊为肝郁脾虚证AIH的患者,同步入组60名与之匹配的健康志愿者,留取血液标本用于检测肝功能及免疫学指标,采用16S rRNA技术检测粪便肠道菌群。依照随机数字表法将60例肝郁脾虚证AIH患者分为西药组(n=30)和西药+逍遥丸组(n=30),两组均服用甲泼尼龙片联合硫唑嘌呤片治疗,后者加用逍遥丸。12周后再次留取血液及粪便标本,观察血清学指标及肠道菌群的改善情况。结果 与健康对照组比较,肝郁脾虚证AIH患者肠道菌群的α多样性及β多样性发生显著改变(P<0.05);该类患者瘤胃球菌科(Ruminococcaceae)、克里斯滕森菌科(Christensenellaceae)、毛螺菌科(Lachnospiraceae)、双歧杆菌科(Bifidobacteriaceae)、梭菌科(Clostridiaceae)显著减少,萨特氏菌属(Sutterella)、屎豆属菌属(Faecalitalea)显著增多,基于上述7个差异菌群构建无创诊断模型,曲线下面积达0.800(95%CI:0.685~0.915)。西药组及西药+逍遥丸组干预12周后,两组均获得了良好的生化应答,但西药+逍遥丸组在降低IgG水平上较西药组更加显著(P<0.05);同时,逍遥丸可显著纠正克里斯滕森菌科、梭菌科、双歧杆菌科、瘤胃球菌科的缺失情况(P<0.05)。结论 肝郁脾虚证AIH患者存在显著的肠道菌群失调,逍遥丸能显著纠正部分肠道菌群,获得较好的生化学应答。

Objective To investigate the effect of Xiaoyao Pill on gut microbiota of autoimmune hepatitis(AIH)patients with liver depression and spleen deficiency syndrome based on"gut-liver axis".Methods Sixty AIH patients with liver depression and spleen deficiency syndrome from Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University were included in this study,along with 60 matched healthy volunteers.Blood specimens were collected for the detection of liver function and immunological indexes,and fecal specimens were used for gut microbiota detection by 16S rRNA technology.According to the random number method,60 AIH patients with liver depression and spleen deficiency syndrome were divided into a western medicine group and a western medicine+Xiaoyao Pill group.Both groups were treated with methylprednisolone combined with azathioprine,with the latter group additionally receiving Xiaoyao Pill.Blood and fecal specimens were collected again after 12 weeks of treatment to observe the improvement of serological indexes and gut microbiota.Results Compared with the healthy control group,theα-diversity andβ-diversity of gut microbiota in AIH patients with liver-depression and spleen-deficiency syndrome were significantly altered(P<0.05).Ruminococcaceae,Christensensenaceae,Lachnospiraceae,Bifidobacteria,and Clostridiaceae were significantly reduced,while Sutterella and Faecalitalea were significantly increased in AIH patients with liver-depression and spleen-deficiency syndrome.A noninvasive diagnostic model was constructed based on the above seven differential bacteria,with an area under the curve of 0.800(95%CI 0.685-0.915).After the western medicine group and the western medicine+Xiaoyao Pill group were treated for 12 weeks,both groups showed good biochemical responses.However,the western medicine+Xiaoyao Pill group had a significant reduction in IgG levels compared to the western medicine group(P<0.05).Moreover,Xiaoyao Pill significantly corrected the deficiencies in the families Christensensenaceae,Clostridiaceae,Bifidobacteriaceae,and Ruminococcaceae(P<0.05).Conclusion Gut microbiota disorder is quite common in AIH patients with liver depression and spleen deficiency syndrome and Xiaoyao Pill can significantly correct part of the gut microbiota and reach a satisfied biochemical response rate.