肝郁肾虚型不明原因复发性流产临床表现与肠道菌群相关性研究

Correlation between Clinical Manifestations and Gut Microbiota of URSA Patients with the Syndrome of Liver Depression and Kidney Deficiency

目的观察健康女性与肝郁肾虚型URSA患者肠道菌群差异,及URSA患者肠道菌群构成与年龄、流产次数、中医证候评分及焦虑-抑郁-紧张量表的关系。方法招募肝郁肾虚型未孕URSA患者28人为观察组,43例正常健康未孕女性为对照组。采集两组一般资料及粪便样本,采用16S rRNA测序,并对测序结果进行多样性分析及物种分析,收集肝郁肾虚型URSA组患者中医证候评分及焦虑-抑郁-紧张评分,并分析其与肠道菌群的关系。结果①Beta多样性分析显示肝郁肾虚未孕URSA患者与健康未孕女性的肠道菌群构成不同。②门水平上,厚壁菌门在两组中含量均为最多,与正常组相比,URSA组中拟杆菌门、变形菌门水平较高,放线菌门水平较低。肝郁肾虚组在属水平上的优势菌,依次为:Faecalibacterium、Bacteroides、Megamonas、Bifidobacterium、Prevotella_9。③在肝郁肾虚组优势菌群中,Glucerabacter与年龄呈正相关,普氏粪杆菌属与流产次数呈正相关,Catenibacterium与抑郁、焦虑、压力、DASS总分呈负相关,Megasphaera与抑郁、中医证候评分呈负相关;在正常组优势菌群中,Erysipelotrichaceae_UCG-003与压力、流产次数呈正相关,双歧杆菌属与中医证候评分呈负相关。结论肝郁肾虚型未孕URSA患者与健康未孕女性肠道菌群构成不同,在门和属水平上,均观察到两组肠道菌群的差异,且差异菌群与URSA患者中医证候评分存在联系,提示肠道菌群可能作为今后肝郁肾虚型URSA诊断和治疗的指标,具有临床意义。

Objective Comparing the differences of gut microbiota between healthy women and URSA patients with the syndrome of liver depression and kidney deficiency,and the relationship between gut microbiota and age,abortion times,TCM syndrome score,and DASS-42 in URSA patients.Exploring the relationship between gut microbiota and clinical symptoms.Methods The observation group was 28 unpregnant URSA patients with the syndrome of liver depression and kidney deficiency,and the control group was 43 healthy unpregnant women.General data and stool samples were collected from two groups.Characterizing the composition of the fecal microbiota using bacterial 16S rRNA gene sequencing.The sequencing results were analyzed for diversity and species.TCM syndrome score and DASS-42 were collected from the URSA group,and the relationship between these scores and gut microbiota was analyzed.Results①Beta diversity analysis shown that the gut microbiota of URSA patients with the syndrome of liver depression and kidney deficiency is different from that of healthy unpregnant women.②At the phylum level,Firmicutes were the most abundant in both groups.Compared with the normal group,the levels of Bacteroidetes and Proteobacteria in the URSA group were higher,and the levels of Actinobacteria were lower.At genus level,the dominant bacteria in URSA group are Faecalibacterium,Bacteroides,Megamonas,Bifidobacterium,Prevotella_9.③In the dominant bacteria of URSA group:Glucerabacter was positively correlated with age,Faecalibacterium was positively correlated with the number of abortions,Catenibacterium was negatively correlated with depression,anxiety,stress,DASS total score,Megasphaera was negatively correlated with depression,TCM syndrome score;In the dominant bacteria of normal group:Erysipelotrichaceae_UCG-003 was positively correlated with stress,the number of abortions,Bifidobacterium was negatively correlated with TCM syndrome score.Conclusion The gut microbiota composition was different between URSA patients with the syndrome of liver depression and kidney deficiency and healthy nonpregnant women,at the phylum and genus levels,the differences in gut microbiota between the two groups were observed,and the differential gut microbiota was associated with URSA patients'TCM syndrome score,suggesting that gut microbiota may be used as an indicator for the diagnosis and treatment of URSA with the syndrome of liver depression and kidney deficiency in the future,which is of clinical significance.