孤独症谱系障碍儿童与健康儿童粪便肠道菌群结构及短链脂肪酸的差异性研究

Difference in fecal intestinal flora instructure and short chain fatty acids between children with autism spectrum disorder and healthy children

目的分析孤独症谱系障碍(ASD)儿童与健康儿童粪便肠道菌群结构及短链脂肪酸变化差异,从肠道菌群角度为ASD的防治提供新思路。方法选取2019年1—11月在江苏大学附属医院被诊断为ASD的25名儿童和同期体检的24名生长发育正常的健康儿童为研究对象,分别为ASD组和对照组。收集其粪便,采用16SrRNA测序分析肠道菌群结构;气相色谱法检测粪便短链脂肪酸含量。结果与对照组比较,ASD组儿童肠道菌群丰富度(Chao1指数及Ace指数)及多样性(Shannon指数)显著降低,差异均有统计学意义(t=2.917、2.890、3.353,P<0.05);门水平上厚壁菌门、变形菌门丰度显著增高,拟杆菌门丰度明显降低,差异均有统计学意义(t=3.180、5.761、5.970,P<0.05);属水平上拟杆菌属、双歧杆菌属、布劳特氏菌属、链球菌属丰度显著降低,梭状芽胞杆菌属、萨特氏菌属丰度显著增加,差异均有统计学意义(Z=2.440、3.100、3.620、3.500、4.200、4.054,P<0.05);粪便短链脂肪酸中乙酸、丙酸及总短链脂肪酸含量显著增高,丁酸含量显著下降,差异均有统计学意义(t=3.040、3.220、2.560、4.100,P<0.05)。相关分析显示双歧杆菌属与丙酸及总短链脂肪酸呈负相关(r=-0.422、-0.412,P<0.05)。结论ASD儿童粪便肠道菌群结构及短链脂肪酸含量发生明显改变,其中双歧杆菌属减少所致丙酸及总短链脂肪酸增高可能与ASD相关。

Objective To investigate the difference in fecal intestinal flora instructure and short chain fatty acids between children with autism spectrum disorder(ASD)and healthy children,so as to provide new clues for the prevention and treatment of ASD from the perspective of intestinal flora.Methods A total of 25 ASD children diagnosed in the Department of Pediatrics,Afficiated Hospital of Jiangsu University were enrolled in the ASD group from January to November 2019.Meanwhile 24 healthy children with typical growth and development who took physical examination were selected as control group.Their feces samples were collected.16 SrRNA sequencing was used to analyze the structure of the intestinal microflora,and gas chromatography was used to detect the content of short-chain fatty acids in feces.Results Compared with the control group,ASD children had a significant decrease in the abundance(Chao index and Ace index)and diversity(Shannon index)of intestinal flora(t=2.917,2.890,3.353,P<0.05),an increase in the abundance of Firmicutes and Proteus and a decrease in the abundance of Bacterioidetes at the phylum level(t=3.180,5.761,5.970,P<0.05).At the genus level,ASD children had a significant decrease in the abundance of Bacterioides,Bifidobacterium,Blautia and Streptococcus,a significant increase in the abundance of Clostridium and Sutterella(Z=2.440,3.100,3.620,3.500,4.200,4.054,P<0.05).Compared with the control group,the levels of acetic acid,propionic acid and total short chain fatty acids in ASD group were significantly increased,while the butyric acid was significantly decreased(t=3.040,3.220,2.560,4.100,P<0.05).Spearman correlation analysis showed Bifidobacterium was negatively correlated with propionic acid and total short chain fatty acids(r=-0.422,-0.412,P<0.05).Conclusions There are significant changes in the structure of intestinal flora and the content of short chain fatty acids in feces of ASD children.The increase of the content of propionic acid and the total short chain fatty acids caused by the decrease of Bifidobacterium may be related to ASD.