Integrated microbiomic and metabolomic analysis of irritable bowel syndrome comorbid with psychiatric symptoms

Abstract

Irritable bowel syndrome (IBS), a chronic functional gastrointestinal disorder, exhibits high comorbidity with psychiatric symptoms. However, a comprehensive evaluation of psychiatric symptoms in IBS and their interactions with the gut microbiota and metabolic disorders is lacking. This study was aimed at investigating the associations among the gut microbiota, serum amino acid metabolites, and different psychiatric comorbidities. Clinical data from 267 patients with IBS and 91 healthy controls (HCs) were collected using validated questionnaires: the IBS Severity Scoring System, Hospital Anxiety and Depression Scale, Patient Health Questionnaire-15, Somatic Symptom Disorder-12, and Symptom Checklist-90 (SCL-90). Patients with IBS were stratified into psychiatric comorbidity and non-comorbidity subgroups based on SCL-90 scores. Serum amino acid metabolites and gut microbiota were analyzed using liquid chromatography-tandem mass spectrometry targeted metabolomics and 16 S rRNA gene sequencing, respectively, followed by integrative correlation analyses to explore associations among microbiota, metabolites, and psychological comorbidities. Patients with IBS showed significantly higher prevalence and severity of psychiatric symptoms than HCs, with obsessive-compulsive symptoms, anxiety, and depression being the most prevalent. Preliminary exploratory multi-omics analyses identified symptom-specific microbial associations: increased Eubacterium ramulus in somatization, decreased Agathobacter and increased Tyzzerella in depression, decreased Peptostreptococcaceae in anxiety, and increased Lactobacillus in hostility. Metabolomic profiling identified 10 differential serum metabolites between IBS and HCs, including elevated L-ornithine, urea, and creatine and reduced arginine, homo-arginine, and S-(5-adenosyl)-L-homocysteine; within the IBS cohort, psychiatric comorbidity subgroups showed elevated arginine-pathway metabolites (L-arginine, Nα-acetyl-L-arginine, and argininosuccinic acid) and reduced aromatic (L-tryptophan and L-phenylalanine), branched-chain (L-valine), and neuroactive (L-glutamate and L-aspartate) amino acids. Several psychiatric symptom-related genera, including Ruminococcus , Agathobacter , and Prevotella , showed associations with various amino acid metabolites. Multi-omic integration identified co-occurrence patterns involving Clostridia and Coriobacteriia with somatization and anxiety symptoms, alongside alterations in ornithine-cycle and glutamatergic metabolites. Because the HC omics group was small, between-group findings have limited power and generalizability and should be interpreted as exploratory. Patients with IBS exhibited multidimensional psychiatric symptoms accompanied by symptom-specific shifts in gut microbiota and serum amino acid profiles. Integrated analyses identified candidate microbiota–metabolite–symptom associations. These exploratory findings provide candidate targets for future longitudinal and mechanistic studies.