Microbiome therapeutics as an innovative concept in IBD

Introduction

IBD, including Crohn`s disease and ulcerative colitis, is characterized by a chronic immune-mediated intestinal inflammation, that is driven by a misled interplay of host-microbial interaction. The identification of microbiota-derived metabolic pathways (Tryptophan, SCFA) in IBD suggest the gut microbiota as a potential key driver of inflammation. As currently the identification of microbial metabolites in IBD mostly relies on associations, a thorough molecular understanding is necessary to unravel underlying host and microbial mechanism that contribute to observed metabolite – phenotype association.

Aims

The objective of the proposed project is to investigate whether specifically targeting gut microbial metabolic functions will serve as a novel concept to enhance therapeutic efficacy in IBD.

The main aims are:

• to identify host and microbial molecular principles that drive metabolic disturbances in IBD
• to in-vitro prioritize metabolic principles using intestinal organoid co-culture models
• to introduce host-microbial metabolic perturbations in mouse models of inflammation
• to assess microbiome-therapy and its immune-metabolic repercussions on host and microbiota in a mouse model of inflammation

Outlook

This outlined experimental approach will serve to identify molecular hubs in host and microbiota that contribute to IBD related metabolic perturbations and might provide actionable entry points for therapeutic interventions. Using in-vivo mouse model testing for microbiome therapeutics, we will provide a proof of concept for the feasibility to restore metabolic perturbations via targeted microbiome therapeutics. This approach might also serve to identify novel immune pathways on host side that might be actionable therapeutic targets for IBD therapy, which act via manipulation of host immunometabolism.