LAUSR

BACKGROUND & AIMS Irritable bowel syndrome (IBS) is a heterogeneous disorder but diagnoses and determination of sub-types are made based on symptoms. We profiled fecal microbiomes of patients with and without irritable bowel syndrome (IBS) to identify biomarkers of this disorder. METHODS We collected fecal and urine samples from 80 patients with IBS (Rome IV criteria; 16-70 years old) and 65 matched individuals without IBS (controls), along with anthropometric, medical, and dietary information. Shotgun and 16S rRNA amplicon sequencing were performed on feces, whereas urine and fecal metabolites were analyzed by gas chromatography and liquid chromatography mass spectrometry. Co-occurrence networks were generated based on significant Spearman correlations between data. Bile acid malabsorption (BAM) was identified in patients with diarrhea by retention of radiolabelled selenium-75 homocholic acid taurine. RESULTS Patients with IBS had significant differences in network connections between diet and fecal microbiomes compared with controls; these were accompanied by differences in fecal metabolomes. We did not find significant differences in fecal microbiota composition among patients with different IBS symptom subtypes. Fecal metabolome profiles could discriminate patients with IBS from controls. Urine metabolomes also differed significantly between patients with IBS and controls, but most discriminatory metabolites were related to diet or medications. Fecal metabolomes but not microbiomes could distinguish patients with IBS with vs those without BAM. CONCLUSIONS Despite the heterogeneity of IBS, patients have significant differences in urine and fecal metabolomes and fecal microbiome from controls, independent of symptom-based subtypes of IBS. Fecal metabolome analysis can be used to distinguish patients with IBS with vs without BAM. These findings might be used to develop microbe-based treatments for these disorders.