LAUSR

Systems biology studies have established that changes in gastrointestinal microbiome composition and function can adversely impact host physiology. Notable diseases synonymously associated with dysbiosis include inflammatory bowel diseases, cancers, metabolic disorders, opportunistic and recurrent pathogen infections. However, there is a scarcity of mechanistic data that advances our understanding of taxonomic correlations with pathophysiologic host-microbiome interactions. Generally, in order to survive a hostile gut environment, microbes are highly metabolically active and produce trans-kingdom signaling molecules to interact with competing microorganisms and the host. These specialized metabolites likely play important homeostatic roles and identifying disease-specific taxa and their effector pathways can provide better strategies for diagnosis, treatment, and prevention, as well as the discovery of innovative therapeutics. The signaling role of microbial biotransformation products such as bile acids, short chain fatty acids, polysaccharides and dietary tryptophan is increasingly recognized, but little is known about the identity and function of metabolites that are synthetized by microbial biosynthetic gene clusters. Here we consider how bioactive natural products directly encoded by the human microbiome can contribute to the pathophysiology of gastrointestinal disease, cancer, autoimmune, antimicrobial-resistant bacterial and viral infections (including COVID-19). We also present strategies used to discover these compounds and the biological activities they exhibit, with consideration of therapeutic interventions that could emerge from understanding molecular causation in gut microbiome research.