维生素D调节肠道菌群改善孤独症谱系障碍儿童临床症状

Vitamin D modulation of intestinal microbiota improves clinical symptoms in children with autism spectrum disorder

摘要

目的 探讨孤独症谱系障碍(ASD)儿童不同维生素D(VD)水平与肠道菌群分布特点,通过补充VD治疗对其肠道菌群分布调节及对临床症状改善。方法 选取2023年5月至2023年9月就诊于西安市人民医院儿童保健科且符合纳入排除标准的ASD儿童77例为研究对象,进行临床症状评估、16S rRNA肠道菌群检测、血清25-羟维生素D[25(OH)D]水平检测.按照血清25(OH)D水平将ASD儿童分为维生素D正常组及维生素D不足组,给予不足组VD补充治疗3月后完成随访复查.采用t检验、Wilcoxon秩和检验进行统计分析及生物信息学方法分析菌群差异。结果 不同VD水平ASD儿童Faecalibacterium、Streptococcus、Lachnospira、Dialister、Fenollaria、Agathobaculum、Coprococcus菌群丰度差异有统计学意义(Z=2.141、2.854、-3.054、-2.084、-2.479、-2.003、-2.805,P<0.05).VD补充治疗前后Lachnospira、Ezakiella及Faecalibacterium丰度差异有统计学意义(Z=3.296、2.668、-3.059,P<0.05).维生素D不足组孤独症行为评定量表(ABC)、儿童孤独症评定量表(CARS)、社交反应量表(SRS)分值(54.26±21.76、33.40±3.86、94.91±22.642)较维生素D正常组高(46.12±19.02、31.94±3.82、93.41±19.92),但无统计学差异(t=0.880、1.370、0.247,P>0.05).补充VD治疗后ASD儿童ABC、CARS、SRS分值降低,但无统计学差异(t=-0.372、-0.057、-0.809,P>0.05)。结论 VD不足影响ASD儿童肠道微生态及其临床症状,通过VD补充治疗可能通过调节ASD儿童肠道微生态,进而改善其临床症状.

Abstract

Objective To explore the relationship between different levels of vitamin D (VD) and the distribution characteristics of intestinal microbiota in children with autism spectrum disorder (ASD), and investigate the regulation of intestinal microbiota distribution and improvement of clinical symptoms through VD supplementation therapy. Methods 77 children diagnosed with ASD who were admitted to the Department of Children's Health Care of Xi'an People's Hospital from May 2023 to September 2023, and who met the inclusion and exclusion criteria, were selected as the study object. Clinical symptom assessment, 16S rRNA gut microbiota detection and serum 25-hydroxyvitamin D [25(OH)D] level detection were performed. Children with ASD were divided into normal VD group and insufficient VD group according to serum 25(OH)D levels. In the insufficient VD group, follow-up examinations were completed after 3 months of VD supplementation therapy. Statistical analysis and bioinformatics methods were used to analyze the differences in microbiota through t-test, Wilcoxon rank-sum test. Results The differences in the abundance of Faecalibacterium, Streptococcus, Lachnospira, Dialister, Fenollaria, Agathobaculum, and Coprococcus microbiota in ASD children with different VD levels were statistically significant (Z=2.141, 2.854, -3.054, -2.084, -2.479, -2.003 and -2.805, respectively, P<0.05). The differences in the abundance of Lachnospira, Ezakiella and Faecalibacterium microbiota before and after VD supplementation treatment were statistically significant (Z=3.296, 2.668 and -3.059, respectively, P<0.05). The autism behavior checklist (ABC), childhood autism rating scale (CARS), and social responsiveness scale (SRS) in the insufficient VD group (54.26±21.76, 33.40±3.86 and 94.91±22.642, respectively) were higher than those in the normal VD group (46.12±19.02, 31.94±3.82 and 93.41±19.92, respectively), but the differences were not statistically significant (t=0.880, 1.370 and 0.247, respectively, P>0.05). After VD supplementation therapy, the ABC, CARS and SRS scores in children with ASD decreased, but the differences were not statistically significant (t=-0.372, -0.057 and -0.809, respectively, P>0.05). Conclusion VD deficiency can affect the intestinal microbiota and clinical symptoms of children with ASD. VD supplementation therapy may improve clinical symptoms by regulating the gut microbiota in children with ASD.

关键词

孤独症谱系障碍 / 肠道菌群 / 25-羟维生素D / 儿童

Key words

autism spectrum disorder / intestinal microbiota / 25-hydroxyvitamin D / children

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基金资助

陕西省科技厅研究项目(2022SFG519)

西安市卫健委研究项目(2021yb21)