Fecal microbiome of patients with ulcerative colitis reflects their phenotype and inflammatory level

Abstract Inflammatory bowel diseases affect ever-increasing numbers of individuals worldwide. Alterations of the intestinal microbiome were reported for Crohn’s disease and at relapse in Ulcerative Colitis (UC); they were not clearly detected in UC at remission. Here we report the characterization of the microbiome by quantitative metagenomics in a cohort of 121 individuals, composed of 65 UC adult patients in remission and 56 healthy controls. A cross-sectional comparison revealed substantial microbiome differences, patients in remission having lower microbiome richness and paucity of the Ruminococcus species driven enterotype. The observed microbiome alterations allowed robust classification of patients by intestinal species abundance, yielding an area under the curve (AUC) of 0.87 in a Receiver-Operator Characteristic (ROC) analysis. Loss of richness was linked to an aggressive UC phenotype and to the importance of past relapses; it was associated with a worse IBD quality of life score (IBDQ-36). Unexpectedly, onset of inflammatory bouts, as assessed by white blood cell count and fecal calprotectin levels, was associated with higher richness; in a longitudinal study of patients at high risk of disease flare, we observed a link between increasing gut microbiome richness over time and calprotectin level, in turn related to clinical inflammatory response and relapse.