Abstract: Objective To analyze the correlation of serum folate acid and vitamin B12 levels with gut microbiota in children with autism spectrum disorder (ASD). Method From January 2020 to February 2021, totally 79 ASD children aged 2 to 7 years and 79 sex- and age-matched neurotypical children in the outpatient department of Chongqing Maternal and Child Health Hospital were enrolled in this study. Serum folate acid and vitamin B12 levels were detected by Chemiluminescence method. The V3-V4 hypervariable regions of bacterial 16SrRNA gene in fecal samples were sequenced. Results Serum folate acid level of children in the ASD group was significantly lower than that of the healthy control group [33.55 (20.47, 39.73) nmol/L vs. 35.50 (27.80, 41.90) nmol/L] (Z=-2.114, P=0.035). Serum vitamin B12 level of children in the ASD group was significantly lower than that of the healthy control group [539.0 (422.50, 702.75) pmol/L vs. 632.0 (519.0, 859.0) pmol/L] (Z=-3.114, P=0.002). There was no difference in the Alpha diversity and Beta diversity of the gut microbiota between the ASD group and control group (P>0.05). In the genus level, ASD children had significantly increasing abundance of Sutterella and Desulfovibrio and decreasing abundance of Bifidobacterium and Rheinheimera compared with the control group (P<0.05). Spearman correlation analysis indicated that serum folate acid level was positively correlated with the abundance of Bifidobacterium (r=0.203) and Prevotella (r=0.179), and negatively correlated with Escherichia abundance (r=-0.223, P＜0.05). Serum vitamin B12 level was positively correlated with the abundance of Bifidobacterium (r=0.172, P=0.048). Conclusion Serum folate acid and vitamin B12 levels are lower in ASD children, which are correlated with the abundance of some gut microbiota.

Key words: autism spectrum disorder, gut microbiota, folic acid, vitamin B12

摘要： 目的 探讨孤独症谱系障碍(ASD)儿童血清叶酸、维生素B12水平与肠道菌群之间的关系。方法 2020年1月—2021年2月在重庆市妇幼保健院门诊调查79例2~7岁ASD 儿童和79例年龄、性别相匹配健康儿童,采用化学发光法检测两组儿童血清叶酸、维生素B12水平,对两组儿童粪便样本中细菌16SrRNA基因的V3-V4高变区进行测序。结果 ASD组血清叶酸水平低于对照组[33.55(20.47,39.73)nmol/Lvs. 35.50(27.80,41.90)nmol/L](Z=-2.114,P=0.035);ASD组血清维生素B12水平低于对照组[539.0(422.50,702.75)pmol/L vs.632.0(519.0,859.0)pmol/L](Z=-3.114,P=0.002)。ASD组和对照组的肠道菌群Alpha多样性、Beta多样性差异无统计学意义(P>0.05)。在属水平,ASD组相比于对照组萨特菌属和脱硫弧菌属的丰度显著提高,双歧杆菌属和莱茵海默氏菌属的丰度显著降低(P<0.05)。Spearman相关性分析显示,血清叶酸水平与双歧杆菌属(r=0.203)、普氏菌属(r=0.179)的丰度呈正相关(P<0.05),与埃希氏菌属丰度呈负相关(r=-0.223,P<0.05)。血清维生素B12水平与双歧杆菌属的丰度呈正相关(r=0.172,P<0.05)。结论 ASD儿童血清叶酸、维生素B12水平较正常儿童下降,且与部分肠道菌群丰度具有相关性。

关键词: 孤独症谱系障碍, 肠道菌群, 叶酸, 维生素B12