Mining the microbiome and microbiota-derived molecules in inflammatory bowel disease

The intestinal microbiota is a complex community that consists of an ecosystem with a dynamic interplay between bacteria, fungi, archaea, and viruses. Recent advances in model systems have revealed that the gut microbiome is critical for maintaining homeostasis through metabolic digestive function, immune regulation, and intestinal barrier integrity. Taxonomic shifts in the intestinal microbiota are strongly correlated with a multitude of human diseases, including inflammatory bowel disease (IBD). However, many of these studies have been descriptive, and thus the understanding of the cause and effect relationship often remains unclear. Using non-human experimental model systems such as gnotobiotic mice, probiotic mono-colonization, or prebiotic supplementation, researchers have defined numerous species-level functions of the intestinal microbiota that have produced therapeutic candidates for IBD. Despite these advances, the molecular mechanisms responsible for the function of much of the microbiota and the interplay with host cellular processes remain areas of tremendous research potential. In particular, future research will need to unlock the functional molecular units of the microbiota in order to utilize this untapped resource of bioactive molecules for therapy. This review will highlight the advances and remaining challenges of microbiota-based functional studies and therapeutic discovery, specifically in IBD. One of the limiting factors for reviewing this topic is the nascent development of this area with information on some drug candidates still under early commercial development. We will also highlight the current and evolving strategies, including in the biotech industry, used for the discovery of microbiota-derived bioactive molecules in health and disease.