非酒精性脂肪性肝病儿童肠道菌群谱的分析研究

Analysis of gut microbiota profile in children with nonalcoholic fatty liver disease

目的探讨儿童非酒精性脂肪性肝病(NAFLD)肠道菌群的结构特征以及肠道菌群与儿童NAFLD发生发展的关系。方法选择2022年1月至12月在云南省第一人民医院确诊、符合入组标准的NAFLD患儿15例作为研究对象,随机选取同期在门诊常规体检的健康儿童15例作为健康对照组,采集所有儿童的身高、体重、腰围、血压、血生化等信息,同时收集两组儿童的粪便标本,利用16S rRNA测序技术进行肠道菌群生物学信息分析。结果NAFLD组中,男8例,女7例,年龄(11.13±1.77)岁,健康对照组中男7例,女8例,年龄(9.73±2.25)岁,两组间性别、年龄、血压差异无统计学意义(P>0.05)。与健康对照组相比,NAFLD组体质量指数、腰围、腰围身高比、丙氨酸氨基转移酶、天门冬氨酸转氨酶、γ-谷氨酰转肽酶、总胆红素、直接胆红素、间接胆红素、低密度脂蛋白胆固醇、尿酸及血清胰岛素升高,而高密度脂蛋白胆固醇明显降低(P<0.05)。物种多样性分析显示,NAFLD组中chaol指数和observed-species指数均明显升高(P<0.05)。物种差异性分析发现,NAFLD组丰度增加的物种包括变形菌门、γ-变形菌纲、肠杆菌目、肠杆菌科、埃希菌-志贺菌属、克雷伯杆菌属、埃希菌-志贺菌属未分类种。健康对照组丰度增加的物种包括:双歧杆菌种、双歧杆菌属、双歧杆菌科、双歧杆菌目、放线菌纲、放线菌门、拟杆菌纲、拟杆菌目、嗜热链球菌种。结论NAFLD患儿存在代谢异常且肠道菌群谱的结构发生明显变化,通过外源性补充双歧杆菌、嗜热链球菌种、拟杆菌属,或许可以预防NAFLD的发生、延缓疾病进展、改善肝内的脂肪沉积。

ObjectiveTo explore the structural characteristics of intestinal microflora in children with non-alcoholic fatty liver disease(NAFLD)and the relationship between intestinal microflora and the occurrence as well as development of NAFLD in children.MethodsFifteen children with NAFLD diagnosed at the First People's Hospital of Yunnan Province from January 2022 to December 2022 were selected as subjects,and 15 healthy children who received routine physical examinations at the outpatient clinic during the same period were randomly selected as healthy control group.The height,weight,waist circumference,blood pressure,blood biochemistry of all children were collected.At the same time,the fresh fecal samples of all children were collected,and the biological information of intestinal flora was analyzed by 16S rRNA sequencing.ResultsIn the NAFLD group,there were eight males and seven females,with an average age of(11.13±1.77)years.In healthy control group,there were seven males and eight females,with an average age of(9.73±2.25)years.There were no significant differences in sex,age,blood pressure between two groups.Compared with the healthy control group,the levels of body mass index,waist circumference,waist-to-height ratio,alanine aminotransferase,aspartate transaminase,gamma-glutamyl transpeptidase,total bilirubin,direct bilirubin,unconjugated bilirubin,low density lipoprotein cholesterol,uric acid and serum insulin significantly increased and high density lipoprotein cholesterol significantly decreased in NAFLD group(P<0.05).The results of species diversity analysis showed that chaol index and observed-species index in NAFLD group were significantly higher than those in healthy control group(P<0.05).Species diversity analysis showed that the species with increased abundance in NAFLD group included:Proteobacteria,Gammaproteobacteria,Enterobacteriaceae,Klebsiella,Escherichia-Shigella,Escherichia-Shigella-unclassified.Differential species with increased abundance in the healthy control group included:Bifidobacterium species,Bifidobacterium,Bifidobacteriaceae,Bifidobacteriales,Actinobacteria,Actinobacteriota,Bacteroidia,Bacteroidales,Streptococcus-thermophilus.ConclusionThere are metabolic abnormalities and obvious changes in the structure of intestinal flora in children with NAFLD.Exogenous supplementation of Bifidobacterium,Streptococcus thermophilus and Bacteroides may prevent the occurrence of NAFLD,delay the progression of disease and improve fat deposition in the liver.