Abstract
Gut microbial and metabolite alterations have been linked to the pathogenesis of inflammatory bowel diseases. Here we perform a multi-omics microbiome and metabolite analysis of a longitudinal cohort of Crohn’s disease patients undergoing autologous hematopoietic stem cell transplantation, and investigational therapy that induces drug free remission in a subset of patients. Via comparison of patients who responded and maintained remission, responded but experienced disease relapse and patients who did not respond to therapy, we identify shared functional signatures that correlate with disease activity despite the variability of gut microbiota profiles at taxonomic level. These signatures reflect the disease state when transferred to gnotobiotic mice. Taken together, the integration of microbiome and metabolite profiles from human cohort and mice improves the predictive modelling of disease outcome, and allows the identification of a network of bacteria-metabolite interactions involving sulfur metabolism as a key mechanism linked to disease activity in Crohn’s disease.
Highlights
Gut microbial and metabolite alterations have been linked to the pathogenesis of inflammatory bowel diseases
Looking at functional modules differentially abundant between patients identified metabolic pathways involved in sulfur transport system and other ion transport systems (e.g. Molybdate and Nickel) to be enriched in active disease, while basic biosynthesis processes are enriched in inactive disease
We investigated perturbations of community structure and metabolic activity in the gut microbiome of Crohn’s disease (CD) patients across longitudinal follow-up sampling after hematopoietic stem cell transplantation (HSCT)
Summary
Gut microbial and metabolite alterations have been linked to the pathogenesis of inflammatory bowel diseases. Via comparison of patients who responded and maintained remission, responded but experienced disease relapse and patients who did not respond to therapy, we identify shared functional signatures that correlate with disease activity despite the variability of gut microbiota profiles at taxonomic level. These signatures reflect the disease state when transferred to gnotobiotic mice. HSCT proved to be successful, potentially by erasing exaggerated immune responses against gut microbes In this cohort, 76% of transplanted CD patients achieved drug-free remission 26 weeks post-transplant
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