Integrated Bile Acid Profile Analysis for The Non-invasive Staging Diagnosis of Ulcerative Colitis

Clinical staging diagnosis and progression tracking for ulcerative colitis (UC) is challenging as poor patient compliance of endoscopic biopsy, we aimed to explore a non-invasive integrative biochemical index to quantitative track and monitor pathological activity. Here we perform a study that integrates bile acid metabolomic profiling, metagenomic sequencing and clinical monitoring on serum and feacal samples from 24 active-state UC patients, 25 remission-state UC patients and 20 healthy volunteers from China. Besides known associations of Fusobacterium nucleatum and Peptostreptococcus stomatis with UC, we found several bile acid-transforming species, including 7-dehydroxygenase and 7/{beta}-dehydrogenase expressing microbiota, were significant correlated with UC pathological activity. We identified 7 microbial gene markers that differentiated active and remission-stage UC and healthy control microbiomes. Relevantly, decreased serum deoxycholic acid /cholic acid ratio and increased fecal ursodeoxycholic acid/chenodeoxycholic acid ratio were associated with pathological activity of UC. Moreover, receiver operating characteristic analysis based on serum/fecal bile acids ratios was much accurate in prediction of active and remission stage outcome. This species-specific temporal change and bile acid dysregulation pattern linked to disease severity indicating that integrated microbiome-bile acid profile maybe implied for disease activity prediction, and that targeting microbiome-mediated restoring gut flora and bile acids homeostasis may be implicative of therapy efficacy. Collectively, these insights will help improve clinical diagnosis and optimize existing medical treatments.