Microbiota-derived metabolites in inflammatory bowel disease

Understanding the role of the gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD) has been an area of intense research over the past decades. Patients with IBD exhibit alterations in their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled to deliver replicable findings across cohorts regarding which microbial species drive the distinct patterns in IBD. The focus of research has therefore shifted to studying the functionality of gut microbes, especially by investigating their effector molecules involved in the immunomodulatory functions of the microbiota, namely metabolites. Metabolic profiles are altered in IBD, and several metabolites have been shown to play a causative role in shaping immune functions in animal models. Therefore, understanding the complex communication between the microbiota, metabolites, and the host bears great potential to unlock new biomarkers for diagnosis, disease course and therapy response as well as novel therapeutic options in the treatment of IBD. In this review, we primarily focus on promising classes of metabolites which are thought to exert beneficial effects and are generally decreased in IBD. Though results from human trials are promising, they have not so far provided a large-scale break-through in IBD-therapy improvement. We therefore propose tailored personalized supplementation of microbiota and metabolites based on multi-omics analysis which accounts for the individual microbial and metabolic profiles in IBD patients rather than one-size-fits-all approaches.