Strategizing the human microbiome for small molecules: Approaches and perspectives

•The microbiome has a composite relationship with its human host through which it modulates numerous biological functions.•The biosynthetic potential of the human microbiome outmatches its known chemical space.•Exploring microbiome-derived small molecules and their biological characterization can guide the discovery of new therapies.•Approaching the microbiome through the use of several evolving strategies may expedite the discovery process.