摘要
目的 探究非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)患儿胆汁酸代谢水平和肠道菌群变化以及二者之间相关性。方法选取云南省第一人民医院儿科诊断为NAFLD的15例儿童为NAFLD组,随机选择相匹配的15例健康儿童为对照组,留取两组儿童清洁粪便标本,采用液相色谱-串联质谱检测胆汁酸代谢水平,并进行肠道菌群16S rRNA基因检测,将差异胆汁酸和肠道菌群进行相关性分析。结果 NAFLD组患儿体质量指数(BMI)、腰围(WC)、腰围身高比(WHtR)、甘油三脂(TG)、天冬氨酸氨基转氨酶(AST)、丙氨酸氨基转移酶(ALT)、低密度脂蛋白胆固醇(LDL-C)、 γ-谷氨酰转肽酶(GGT)、总胆红素(TBIL)、直接胆红素(UBIL)、间接胆红素(DBIL)、尿酸(UA)、血红蛋白(HGB)水平显著高于对照组,而高密度脂蛋白胆固醇(HDL-C)水平低于对照组(均P<0.05)。NAFLD组患儿脱氧胆酸(DCA)、鹅脱氧胆酸(CDCA)、别胆酸(ACA)、6,7-二酮石胆酸(6,7-diketoLCA)水平显著升高,熊去氧胆酸(UDCA)、6-酮石胆酸(6-ketoLCA)、猪胆酸(HCA)、熊去氧胆酸硫酸(UDCA-3S)水平显著降低,且组间差异均有统计学意义(均P<0.05)。与对照组比较,NAFLD组患儿肠道变形菌门丰度增高,放线菌门、拟杆菌门丰度下降(均P<0.05)。与对照组比较,NAFLD组患儿肠道双歧杆菌属丰度降低,埃希-志贺菌属丰度升高(均P<0.05)。相关性分析显示,髌骨菌门与CDCA、鹅去氧胆酸-3-β-葡糖苷酸(CDCA-3Gln)呈正相关(均P<0.05)。埃希-志贺菌属与UDCA、熊果胆酸(UCA)、ACA、GDHCA、CDCA-3S具有显著相关性(均P<0.05)。乳杆菌属与UDCA、ω-鼠胆酸(ωMCA)、ACA、鹅去氧胆酸硫酸(CDCA-3S)、牛磺石胆酸(TLCA)具有显著相关性(均P<0.05)。结论 NAFLD患者胆汁酸代谢水平及肠道菌群组成发生显著变化,且差异胆汁酸与肠道菌群存在显著相关性。胆汁酸代谢水平及肠道菌群的结构改变对预测NAFLD具有积极意义。
Objective To observe the changes in level of bile acid metabolism,gut microbiota,and the relevance with nonalcoholic fatty liver disease(NAFLD).Methods A total of 15 children diagnosed with NAFLD in the Department of Pediatrics of our hospital were enrolled,randomly selected matched 15 healthy children as control group.Clean stool specimens of the two groups of children were collected,and the level of bile acid metabolism was detected using ultra-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS),while 16S rRNA gene sequencing was utilized to detect and test the intestinal flora of the two groups of children.The differences in bile acids and intestinal flora were subject to correlation analysis.Results The average body mass index(BMI),waist circumference(WC),waist-to-height ratio(WHtR),triglyceride(TG),aspartate transaminase(AST),alanine aminotransferase(ALT),low density lipoprotein cholesterol(LDL-C),gamma-glutamyl transpeptidase(GGT),total bilirubin(TBIL),unconjugated bilirubin(UBIL),direct bilirubin(DBIL),uric acid(UA),and the amount of bilirubin and blood stream hemoglobin(HGB) significantly increased in the NAFLD group;high-density lipoprotein cholesterol(HDL-C) was lower than that in the control group(all P<0.05).Comparison of bile acid content between groups showed that the concentrations of deoxycholic acid(DCA),chenodeoxycholic acid(CDCA),allocholic acid(ACA) and 6,7-diketolithocholic acid(6,7-diketoLCA) in the NAFLD group elevated,while ursodeoxycholic acid(UDCA),6-ketolithocholic acid(6-ketoLCA),hyocholic acid(HCA),and ursodeoxycholic acid 3-Sulfate(UDCA-3S) decreased in contrast to those in the control group,respectively(all P<0.05).Compared with control group,the mean abundance of Proteobacteria in NAFLD group increased,while those of Actinobacteriota and Bacteroidota reduced(all P<0.05).Compared with control group,Bifidobacterium was found to be inferior while Escherichia-Shigella be superior to those in the NAFLD group respectively(all P<0.05).Correlation analysis showed that there were positive correlation between Patellobacteria and CDCA and chenodeoxycholic acid-3-β-D-Glucuronide(CDCA-3Gln)(all P<0.05).There were significant correlation between Escherichia-Shigella and UDCA,UCA,ACA,GDHCA and CDCA-3S(all P<0.05),and significant correlation between Lactobacillus and UDCA,ω-muricholic acid(ωMCA),ACA,CDCA-3S and taurolithocholic acid(TLCA)(all P<0.05).Conclusion Significant changes occurred in the level of bile acid metabolism and intestinal flora composition in patients with NAFLD,and there is a correlation between differential bile acid profiles and intestinal flora.Structural changes in level of bile acid metabolism and intestinal flora may have positive significance in predicting the occurrence of NAFLD.
作者
张学敏
马瑞雪
代怡琳
李桂仙
罗婉榕
田云粉
ZHANG Xuemin;MA Ruixue;DAI Yilin;LI Guixian;LUO Wanrong;TIAN Yunfen(Medical College of Kunming University of Science and Technology,Kunming,Yunnan 650032,China;不详)
出处
《中国微生态学杂志》
CAS
CSCD
北大核心
2024年第10期1187-1194,1201,共9页
Chinese Journal of Microecology
基金
昆明医科大学应用基础研究联合专项(202201AY070001-253)。
关键词
非酒精性脂肪性肝病
儿童
胆汁酸代谢水平
靶向代谢组学
肠道菌群
Nonalcoholic fatty liver disease
Child
Levels of bile acid metabolism
Targeted metabolomics
Gut microbiota