乙型肝炎肝硬化患者伴或不伴腹水对肠道菌群的影响 栾雨婷

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菌属和假丁弧菌属的丰度显著降低( P 值分别为 < 0. 01、 < 0. 001) ,肠杆菌属、大肠埃希菌属和韦荣球菌属的丰度显著增加( P 值分
别为 < 0. 05、 < 0. 001、 < 0. 01) 。 大肠埃希菌属和韦荣球菌属均与 CTP 评分、凝血酶原时间和国际标准化比率( INR) 均呈正相关,
与血清 Alb 水平均呈负相关( P 值均 < 0. 05) 。 假丁弧菌属、norank_f_毛螺菌科、unclassified_f_毛螺菌科、布劳特氏菌属与 Alb 水平
均呈正相关,与 CTP 评分和 C 反应蛋白水平均呈负相关( P 值均 < 0. 05) 。 KEGG 通路分析显示,伴随腹水的出现,与转录相关蛋
收 基 作doi者稿 金:1简日 项0.介期 目39:::62究栾国90/2。雨家j0. i二婷自s-s0n(者然1.11对科9-09012本学12-;文基-修)5贡金,2回女5献面6日,.相上主2期0同项要2:02,目从.0同02资事70为.助-中0第10(医52一81-药作517防3者3。9治4。8慢;8性18肝74病39的0)临床研究;蔡文君(1991 - ),女,主要从事中医药防治慢性肝病的基础与临床研 通信作者:慕永平,电子信箱:ypmu8888@ 126. 。 com
摘要:目的 方法 探讨乙型肝炎肝硬化(HBLC)伴有或不伴有腹水患者肠道菌群的差异。
收集 2016 年 10 月 - 12 月于上海
中医药大学附属曙光医院肝硬化科就诊的 HBLC 患者 57 例,其中无腹水 30 例( HBLC - WOA) ,有腹水但无 SBP 27 例( HBLC -
WA) ,并纳入 28 例健康志愿者( HC) ,采用 16S rRNA 测序技术,比较两组肝硬化患者间肠道菌群的分布差异。 计数资料 2 组间比
, , , , , , , , , , LUAN Yuting CAI Wenjun JIANG Shili ZHAO Changqing GU Hongtu YUAN Jili XING Feng LYU Jing LIU Chenghai LIU Ping ( ; , MU Yongping. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Institute of Liver Diseases Shanghai ; ; University of Traditional Chinese Key Laboratory of Liver and Kidney Diseases of the Ministry of Education Shanghai Key Laboratory of Tra ; , ) ditional Chinese Clinical Medicine Shanghai 201203 China
栾雨婷,等. 乙型肝炎肝硬化患者伴或不伴腹水对肠道菌群的影响
1521
( ) ( ) Pfdr < 0. 05 was considered statistically significant. The Spearman rank correlation test was used for correlation analysis. An analysis of simi
larity ANOSIM and a non - parametric multivariate analysis of variance Adonis were used for comparison between groups under different
( ) conditions. Results The abundance of fecal microbiota gradually decreased with the appearance of ascites in HBLC patients P = 0 042 . ( : , ; : There were significant differences between the HBLC - WOA group and the HC group ANOSIM R = 0. 159 P = 0. 001 Adonis R2 = , ) ( : , ; : , 0 067 P = 0. 001 and between the HBLC - WA group and the HC group ANOSIM R = 0. 323 P = 0. 001 Adonis R2 = 0. 107 P = ) , , 0 001 . At the genus level compared with the HC group the HBLC - WA group had significant reductions in the abundance of Subdoli ( ) , , granulum and Pseudobutyrivibrio P < 0. 01 and P < 0. 001 and significant increases in the abundance of Enterobacter Escherichia and ( , , ) Veillonella P < 0. 05 P < 0. 001 and P < 0. 01 . Escherichia and Veillonella were positively correlated with Child - Turcotte - Pugh ( ) , , ( ) ( CTP score prothrombin time and international normalized ratio and were negatively correlated with serum albumin Alb level all P < ) , , , 0. 05 . Pseudobutyrivibrio norank_f_Lachnospiraceae unclassified_f_Lachnospiraceae and Blautia were positively correlated with Alb ( ) level and were negatively correlated with CTP score and C - reactive protein level all P < 0. 05 . The KEGG pathway analysis showed that , , with the appearance of ascites there were gradual increases in the abundance of the pathways associated with transcription - related proteins , , , ( ), alpha - linolenic acid metabolism Staphylococcus aureus infection bacterial invasion of epithelial cells and bile secretion all Pfdr < 0. 05 ( ) as well as a gradual reduction in the abundance of the pathway associated with the biosynthesis of flavonoids Pfdr < 0. 05 . The pathway as ( ), sociated with bacterial invasion of epithelial cells was positively correlated with the abundance of Escherichia P < 0. 001 and the abun ( ) dance of Enterobacter was positively correlated with the pathway of bile secretion P < 0. 001 . Conclusion Intestinal flora disturbance is , observed in HBLC - WA patients featuring the reductions in the abundance of Subdoligranulum and Pseudobutyrivibrio belonging to Firmi
the Kruskal - Wallis H test was used for comparison of continuous variables between more than two groups. Multiple hypothesis tests were
( ), used for comparison of relative abundance between species and was adjusted by Benjamini and Hochberg false discovery rate fdr and
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临床肝胆病杂志第 卷第期 年月 , , 36 7 2020 7 J Clin Hepatol Vol.36 No.7 Jul.2020
乙型肝炎肝硬化患者伴或不伴腹水对肠道菌群的影响
栾雨婷,蔡文君,蒋轼丽,赵长青,顾宏图,袁继丽,邢 枫,吕 靖, 刘成海,刘 平,慕永平
上海中医药大学附属曙光医院,上海中医药大学肝病研究所,教育部肝肾疾病重点实验室, 上海市中医临床重点实验室,上海201203
, ( ) Medicine from October to December 2016 were enrolled among whom 30 had no ascites HBLC - WOA group and 27 had ascites without ( )( ), ( ) spontaneous peritonitis SBP HBLC - WA group and 28 healthy volunteers were enrolled as healthy controls HC group . Intestinal
Fra Baidu bibliotek
较采用 Wilcoxon 秩和检验;计量资料 2 组间比较采用 Mann - Whitney U 检验,3 组比较采用 Kruskal - Wallis H 检验。 组间各物种相
对丰度差异的比较采用多重假设检验,采用 Benjamini 和 Hochberg 错误发现率( fdr) 进行调整,Pfdr < 0. 05 为差异有统计学意义。
flora was compared between the two groups of HBLC patients using 16S rRNA sequencing. The Wilcoxon rank sum test was used for compari
, ; son of categorical data between two groups and the Mann - Whitney U test was used for comparison of continuous data between two groups
相关分析采用 Spearman 秩相关检验。 不同条件下组间的差异比较采用相似性分析( ANOSIM) 和非参数多元方差分析( Adonis) 。
结果 伴随腹水的出现,HBLC 患者粪便微生物群的多样性降低( P = 0. 042) 。 PCoA 结果显示,HBLC - WOA 组、HBLC - WA 组与
关键词:乙型肝炎; 肝硬化; 腹水; 胃肠道微生物组 中图分类号:R512. 62 文献标志码:A 文章编号: ( ) 1001 - 5256 2020 07 - 1520 - 07
A comparative study of intestinal flora between hepatitis B cirrhosis patients with or without ascites
白、α - 亚油酸代谢、金黄色葡萄球菌感染、细菌侵袭上皮细胞和胆汁分泌通路相关的菌群丰度逐渐上升( Pfdr 值均 < 0. 05) ,而与黄
酮类生物合成通路相关的菌群丰度逐渐下降 ( Pfdr < 0. 05) 。 且细菌侵袭上皮细胞通路与大肠 埃 希 菌 属 的 丰 度 呈 正 相 关 ( P <
: ( ) Abstract Objective To investigate the difference in intestinal flora between hepatitis B liver cirrhosis HBLC patients with or without
ascites. Methods A total of 57 patients with HBLC who visited Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese
结论 0 001) ,肠杆菌属丰度与胆汁分泌通路呈正相关( P < 0. 001) 。
HBLC - WA 患者肠道菌群紊乱以硬壁菌门的罕见小球菌属
和假丁弧菌属丰度降低,变形菌门的肠杆菌属和大肠埃希菌属丰度增加为特征,肠杆菌可能参与胆汁分泌通路,大肠埃希菌可能参
与上皮细胞的细菌侵袭通路,提示对于无 SBP 的 HBLC - WA 患者,调节肠道菌群的同时,可能也要考虑 SBP 的预防性治疗。
HC 组间比较差异有统计学意义( HBLC - WOA vs HC, ANOSIM: R = 0. 159, P = 0. 001, Adonis: R2 = 0. 067, P = 0. 001; HBLC -
WA vs HC, ANOSIM: R = 0. 323, P = 0. 001, Adonis: R2 = 0. 107, P = 0. 001) 。 在属水平上,与 HC 组比较,HBLC - WA 组罕见小球
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