Analysis Of Gut Microbiota Characteristics And Drug Therapy Associations In Children With Attention-deficit Hyperactivity Disorder

Objective: To compare the difference of gut microbiota between children with attention deficit hyperactivity disorder(ADHD)and normal children,and investigate the changes of gut microbiota in ADHD children after taking methylphenidate,and explore the relationship between gut microbiota and behavior changes in children with ADHD before and after taking medicine.Methods: We Choose 18 school-age children diagnosed with ADHD newly as ADHD group,10 normal children of the same age as the control group.Stool samples of ADHD were collected after diagnosis as group A1,that after taking methylphenidate for more than one month as group A2,and stool samples of normal children as group B.High-throughput sequencing that based on the 16 S rRNA was used to analyze the composition of gut microbiota in the three groups.The correlation between gut microbiota and behavior changes was analyzed in 7 children in ADHD group who completed Vanderbilt scale before and after taking medicine.Results: Compared with group B,the Shannon index of group A1 andgroup A2 decreased(P(27)0.05).LEfSe analysis of children in group A1 and group A2 showed,3 microbiota were significantly enriched in group A1,which were Bacillales,Family_XI_o__Bacillales and Gemella;Bacteroidetes,Bacteroidia and Bacteroidales were significantly enriched in A2 group.The analysis of the difference between group A1 and group B showed the abundance of Rhodococcus,Lachnospiraceae_ND3007_group and Parabacteroides in group A1 was lower than that in group B,the abundance of Enterobacter and Citrobacter was higher at the genus level(P(27)0.05).After correcting the confounding factors,the difference of gut microbiota was still statistically significant(P(27)0.05).The analysis of the difference between group A1 and group A2 showed the Gemella abundance in A1 group was higher than that in A2 group at the genus level(P(27)0.05).The correlation analysis between the changes of gut microbiota and ADHD behavior in 15 ADHD children who completed the Vanderbilt scale before and after treatment showed that the abundance of Gemella decreased and the behavior of ADHD improved after treatment(P(27)0.05).The abundance of Gemella was positively correlated with the level of attention deficit(the number of items,r=0.564,P=0.029;the total score,r=0.517,P=0.048),hyperactivity impulse(the total score,r=0.537,P=0.039)and function impairment(the total score,r=0.525,P=0.045).Conclusion: The decrease of microbial Alpha diversity in ADHD may reduce the level of GABA and BDNF produced by bacteria,increase thehyperactive and impulsive behavior of the host.At the genus level,compared with normal children,the increasing abundance of Enterobacter and Citrobacter in ADHD increased the levels of endotoxin released and indole producted,the brain function changed,which affected the behavior of the host.the decreasing abundance of Parabacteroides decreased the integrity of gray and white matter in their hippocampus and internal capsule,decreased their learning ability and increased the level of hyperactivity.Taking methylphenidate increased the abundance of Bacteroidetes,the level of SCFAs and BDNF in ADHD,improved the symptoms of attention deficit and hyperactivity.The abundance of Gemella decreased after treatment in ADHD,and the abundance of Gemella was positively correlated with the level of attention deficit and hyperactivity.