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孤独症谱系障碍患儿不同血清总25-羟维生素D水平与肠道菌群的差异性研究

Differences of Intestinal Flora in Children with Autism Spectrum Disorder with Different Levels of Serum Total 25-hydroxyvitamin D

    摘要
  • 摘要:
      目的  探究孤独症谱系障碍(autism spectrum disorder，ASD)患儿维生素D正常与缺乏状态下的肠道菌群差异及血清总25-羟维生素Dtotal 25-hydroxyvitamin D，T-25(OH)D水平与肠道菌群的相关性。
      方法  回顾性纳入2019年10月至2022年2月于北京协和医院风湿免疫科门诊就诊的1~12岁ASD患儿的临床资料。采用液相色谱串联质谱法检测ASD患儿的血清T- 25(OH)D水平，并根据血清T- 25(OH)D水平将其分为维生素D正常组T-25(OH)D＞30 μg/L、不足组20 μg/L≤T-25(OH)D ≤30 μg/L和缺乏组T-25(OH)D＜20 μg/L。应用生物信息学方法分析ASD患儿的肠道宏基因组测序结果。
      结果  共46例符合纳入和排除标准的ASD患儿纳入本研究，维生素D正常组、不足组、缺乏组分别为15例、16例、15例。线性判别分析发现，维生素D缺乏组的沃氏嗜胆菌、Adlercreutzia equolifaciens、Asaccharobacter celatus、大肠埃希菌显著升高；而脆弱拟杆菌和Hungatella hathewayi丰度显著降低。沃氏嗜胆菌和Adlercreutzia equolifaciens丰度与血清T- 25(OH)D水平均呈负相关(r=-0.45, fdr=0.055, P=0.002; r=-0.44, fdr=0.055, P=0.003)；脆弱拟杆菌丰度与血清T- 25(OH)D水平呈正相关(r=0.42, fdr=0.073, P=0.004)。
      结论  ASD患儿的维生素D缺乏状态可能加重肠道菌群紊乱，血清T-25(OH)水平降低可能使潜在有害菌定植增加、益生菌定植减少。本研究为ASD患儿积极补充维生素D提供了证据支持。

     

    Abstract:
      Objective  To investigate the differences of intestinal flora in Vitamin D adequacy and deficiency groups of children with autism spectrum disorder(ASD) and the correlation between serum total 25-hydroxyvitamin D T-25(OH)D levels and intestinal flora.
      Methods  ASD children who attended the outpatient clinic of the department of Rheumatology and Clinical Immunology of Peking Union Medical College Hospital during October 2009 and February 2022 were retrospectively included in the study. According to the serum T-25(OH)D levels, they were divided into Vitamin D adequacy groupT-25(OH)D > 30 μg/L, Vitamin D insufficiency group20 μg/L≤T-25(OH)D≤30 μg/L and Vitamin D deficiency groupT-25(OH)D < 20 μg/L.Serum T-25(OH)D levels were measured using liquid chromatography-tandem mass spectrometry. Human gut metagenome data from these children with ASD were analyzed using bioinformatics methods.
      Results  46 children with ASD who met the inclusion and exclusion criteria were included in the study. The numbers of patients in Vitamin D adequacy group, Vitamin D insufficiency group and Vitamin D deficiency group were respectively 15, 16 and 15. Linear discriminant analysis revealed that the bacteria abundance of Bilophila wadsworthia, Adlercreutzia equolifaciens, Asaccharobacter celatus and Escherichia coli were significantly enriched, while the bacteria abundance of Bacteroides fragilis and Hungatella hathewayi were significantly lower in the Vitamin D deficiency group. The relative abundance of Bilophila wadsworthia and Adlercreutzia equolifaciens were negatively correlated with serum T-25(OH)D levels(r=-0.45, fdr=0.055, P=0.002;r=-0.44, fdr=0.055, P=0.003), and the relative abundance of Bacteroides fragilis was positively correlated with serum T-25(OH)D levels (r=0.42, fdr=0.073, P=0.004).
      Conclusions  Vitamin D deficiency in ASD may exacerbate ASD flora disorders, and decreased serum T-25(OH)D levels may facilitate potentially harmful bacteria but inhibit probiotic colonization. This study provides partial evidence that children with ASD should be actively supplemented with vitamin D.

     

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