PR002477 (Project)

Description:Background: Irritable Bowel Syndrome (IBS), a chronic functional gastrointestinal disorder, shows high comorbidity rates with psychiatric disorders. However, comprehensive evaluations of psychiatric symptoms in IBS and their interactions with gut microbiota and metabolic disorders are lacking. This study aims to investigated mechanistic links among gut microbiota, serum amino acid metabolites, and differently psychological comorbidities. Methods: Clinical data from 267 IBS patients and 91 healthy controls (HCs) were collected using validated questionnaires: IBS Severity Scoring System (IBS-SSS), Hospital Anxiety and Depression Scale, Patient Health Questionnaire-15 (PHQ-15), Somatic Symptom Disorder-12 (SSD-12), and Symptom Checklist-90 (SCL-90). IBS patients were stratified into psychiatric comorbidity and non-comorbidity subgroups based on SCL-90 scores. Serum amino acid metabolites and gut microbiota were analyzed using LC-MS/MS targeted metabolomics and 16S rRNA gene sequencing, respectively. followed by integrative correlation analyses to explore interactions among microbiota, metabolites, and psychological comorbidities. Results: IBS patients showed significantly higher prevalence rates of all assessed psychiatric disorders compared to HCs, with somatization, anxiety, obsessive-compulsive traits, and depression as predominant manifestations. IBS patients with different psychiatric comorbidities exhibit distinct gut microbiota compositions, including altered abundances of the class Clostridia (e.g., Ruminococcus, Faecalibacterium, Monoglobus), the class Coriobacteriia (e.g., Collinsella), and the class Bacilli (e.g., Lactococcus, Erysipelatoclostridium). Metabolomic profiling revealed elevated arginine and its derivatives (Nα-acetyl-L-arginine, argininosuccinate, succinate) and reductions in aromatic amino acids (L-tryptophan, L-phenylalanine, L-tyrosine), branched-chain amino acids (L-valine, L-leucine, L-isoleucine), and neuroactive amino acids (L-glutamate, L-aspartate). Multi-omics integration implicated Clostridia and Coriobacteriia might respectively participate in the pathophysiology of somatization and anxiety comorbidities by modulating the ornithine cycle and glutamatergic metabolism. Conclusions: IBS patients exhibit multidimensional psychiatric disorders, with distinct gut microbiota and serum amino acids profiles corresponding to specific psychiatric comorbidities. The interaction between gut microbiota and amino acids may be involved in the pathogenesis of IBS with comorbid mental disorders. This study provide novel targets for early stratification and precision interventions in IBS with psychological comorbidities.