| Objective: Obsessive-compulsive disorder(OCD)is a disabling mental disorder with unknown etiology,the relationship between the occurrence and development of OCD and intestinal flora has not been fully elucidated.This study aims to through 16 Sr RNA sequencing,metagenomics and metabonomics Multiple omics analysis,for starting the drug has not whether there was a child and adolescent patients intestinal disorders provide direct evidence and comprehensive understanding,and finding potential biomarkers associated with OCD,reveals the pathophysiological mechanism,to explore the diagnosis and treatment of SSRIs influence on the intestinal flora,It provides an important theoretical basis for the early diagnosis and prognosis of obsessive-compulsive disorder.Methods: 1.Stool samples were collected from 49 first-episode untreated children and adolescents with OCD and 42 age-and sex-matched healthy controls(HC),and all subjects were evaluated for clinical parameters.2.Fecal samples from 49 patients with OCD and 42 HCs were analyzed by 16 S r RNA sequencing.3.Fecal samples from 19 OCD and 18 HC subjects were analyzed by Illumina Hi Seq sequencing platform using metagenomic high-throughput sequencing method.4.Correlation analysis was conducted between metagomic sequencing results and clinical parameters to explore the relationship between intestinal flora and OCD symptoms and the possible functional pathways involved in the pathogenesis.5.Fecal samples from 49 cases of OCD,42 cases of HC a were analyzed by metabonomic method based on UHPLS-MS.6.Association analysis was performed on metagenomic and metabonomics analysis data to clarify the association between differential flora and differential metabolites.7.Using 16 S r RNA sequencing,macrogenomics and metabonomics methods,the stool samples of 26 patients with OCD who had been treated with SSRIs for 12 weeks(OCD12W)were analyzed by multigroup analysis,to explore the characteristics of intestinal flora changes before and after treatment(OCD0W-OCD12W),and to find specific microbial markers and metabolic pathways that may be involved in the treatment effect.Results: 1.The diversity index of intestinal flora in patients with OCD was significantly decreased(obs,P<0.001;chao1,P<0.001;ACE,P<0.001;shannon,P<0.001;simpson,P<0.05;good,P<0.001),and the microbial interaction network was significantly weaker than that in HC group.2.The relative abundance ratio(F/B)of Firmicutes /Bacteroidetes in OCD group was significantly lower(P<0.001).3.The abundance of butyrate-producing bacteria such as Romboutsia(q<0.01),Mitsuokella(q<0.01),and Terrasporobacter(q<0.01)in the intestine of patients with OCD decreased significantly.4.The random forest model identified 30 specific bacteria as markers,and the AUC between OCD patients and HC was 0.9011.5.There is a correlation between the changes of clinical parameters in OCD group and the abundance of specific bacteria in intestinal flora.6.A total of 43 endogenous differential metabolites were screened out in OCD-HC group,and there was a correlation between the differential metabolites and the differential flora(P<0.05).7.The relative contents of Neopterin and Sepiapterin,the intermediate products of folate biosynthesis,were significantly higher in OCD group(P<0.05);Glucocorticoids and corticosterones significantly decreased in regulating lipolysis in adipocytes and prion diseases(P<0.05).8.There was no significant difference in the diversity index of intestinal flora in patients with obsessive-compulsive disorder(OCD12W)after drug intervention compared with those in the pre-intervention group(OCD0W)(P>0.05).9.The random forest model identified 13 specific bacteria as microbial markers in patients in the treatment effective group(Respond)and non-response group(Nonrespond),with AUC of 0.8274.10.A total of 63 different metabolites were screened in the OCD0W-OCD12 W group,among which the relative contents of neopterin and Sepiapterin,the intermediate products of folate biosynthesis,were significantly reduced in the OCD12 W group(P<0.05);The metabolites involved in amino acid biosynthesis pathway such as fumarate,2-oxyisovalerate and3-dehydroquinic acid(DHQ)were significantly increased(P<0.05).Conclusion: 1.The diversity of intestinal flora in the first episode of children and adolescents with obsessive-compulsive disorder without medication was significantly reduced,and the microbial interaction network had obvious defects.2.The destruction of intestinal homeostasis in children and adolescents with OCD without drugs for the first time is related to the significant decrease in the abundance of butyrate producing bacteria such as Romboutsia.3.The OCD and HC groups can be distinguished by the specific intestinal microflora biomarkers dominated by Bordetella,and the efficacy of drug intervention can also be predicted by the specific biomarker model dominated by Actinospica.4.There is a correlation between the changes of clinical parameters and the abundance of specific species of intestinal flora in the first untreated children and adolescents with OCD.5.Many metabolic pathways such as glycolipid metabolism,amino acid metabolism and steroid biosynthesis of intestinal flora in children and adolescents with OCD were damaged.6.Short-term SSRIs treatment can improve the clinical symptoms of children and adolescents with OCD,but it can not significantly change the composition and structure of intestinal microflora. |
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