孤独症谱系障碍儿童肠道菌群与症状严重程度相关性研究

Correlation between gutmicrobiota and symptom severity in children with autism spectrum disorder

目的分析孤独症谱系障碍(ASD)儿童肠道菌群结构特点及与症状严重程度的相关性,以期为ASD发病机理及靶向治疗提供新思路。方法选取2021年3月—2021年9月在珠海市妇幼保健院儿童心理卫生科就诊的107名ASD儿童作为ASD组,纳入幼儿园正常儿童30名作为对照组。采用儿童孤独症评定量表评估ASD症状严重程度。收集两组儿童新鲜粪便并提取样本DNA,对细菌16S rDNA V4区进行扩增并进行高通量测序。结果ASD组和对照组儿童的肠道菌群α多样性指数和β多样性差异无统计学意义(P>0.05);在门水平,ASD组儿童变形菌门相对丰度较对照组儿童低,且差异具有统计学意义(t=-3.103,P<0.05);在科水平,ASD组儿童的优势菌群为坦纳氏菌科、爱格士氏菌科、脱硫弧菌科、莫拉氏菌科、月形单胞菌科、双歧杆菌科;正常儿童的优势菌群为恩斯氏菌科、链球菌科、巴斯德氏菌科;在属水平,不同症状严重程度儿童丁酸弧菌属、柯林斯氏菌属、布劳特氏菌属、巨单胞菌属相对丰度差异均有统计学意义(P<0.05);Spearman相关性分析显示,ASD儿童布劳特氏菌属和巨单胞菌属与CARS评分呈正相关(r=0.213、0.288,P<0.05)。结论ASD儿童存在肠道菌群紊乱,且肠道菌群结构与行为症状的严重程度密切相关。

Objective To analyze structural characteristics of gut microbiota and its correlation with symptom severity in children with autism spectrum disorder(ASD),in order to provide new ideas for exploring pathogeny and targeted therapy.Methods A total of 107ASD children in the Child Mental Health Department of Zhuhai Maternal and Child Health Hospital from March 2021to September 2021were selected as the ASD group,and 30normal preschool children in a kindergarten were included as the control group.The severity of ASD symptoms was assessed using the Childhood Autism Rating Scale(CARS).Sample DNA was extracted after collecting fresh stools from both groups of children,and then the 16SrDNA V4region of the bacteria was amplified and sequenced in high throughput.Results There was no significant difference between the alpha diversity index and beta diversity of the gut microbiota between children in ASD group and control group(P>0.05).At the phylum level,the relative abundance of the Proteobacteria in the ASD group was significantly lower than that in the control group(t=-3.103,P<0.05).At the family level,the dominant gut microbiota of children in ASD group included Tannerellaceae,Eggerthellaceae,Desulfovibrionales,Selenomonadaceae,Moraxellaceae,Bifidobacterium,while the dominant gut microbiota in normal group included Barnesiellaceae,Streptococcus,Barnesiella.At the genus level,the differences in the relative abundance of Anaerostipes,Collinsella,Blautia,and Megamonas in children with different severity of symptoms were statistically significant(P<0.05).Spearman correlation analysis showed a positive correlation of Blautia and Megamonas with CARS score in ASD children(r=0.213,0.288,P<0.05).Conclusion Gut microbiota of ASD children is disturbed and its structure is strongly related to the severity of behavioral symptoms.