Integrated microbiota and metabolite profiles link Crohn's disease to sulfur metabolism.
Amira MetwalyAndreas DunkelNadine WaldschmittAbilash Chakravarthy Durai RajIlias LagkouvardosAna Maria CorralizaAida MayorgasMargarita Martinez-MedinaSinah ReiterMichael SchloterThomas HofmannMatthieu AllezJulian PanesAzucena SalasDirk HallerPublished in: Nature communications (2020)
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.
Keyphrases
- disease activity
- systemic lupus erythematosus
- rheumatoid arthritis
- ankylosing spondylitis
- rheumatoid arthritis patients
- patients undergoing
- stem cells
- clinical trial
- end stage renal disease
- randomized controlled trial
- ejection fraction
- chronic kidney disease
- microbial community
- juvenile idiopathic arthritis
- genome wide
- high fat diet induced
- mesenchymal stem cells
- insulin resistance
- free survival