Abstract
Covering: 2015 to 2025Chemical crosstalk is universal to all life, niche-specific, and essential to thrive. This crosstalk is mediated by a large diversity of molecules, including metal ions, small molecules, polysaccharides, nucleic acids, lipids, and proteins. Among these, specialized small molecules referred to as natural products (NPs) play an important role in microbe-drug/environment interactions, microbe-microbe, and microbe-host interactions. Microbial communication using NPs allows microbes to sense quorum, form biofilms, eliminate competition, establish symbiosis, evade immune attack, and respond to stress. In most cases, the elucidation of small molecule mediators and effectors of microbe-host interactions presents a major challenge due to the relatively low abundance of microbial metabolites in a milieu of host, microbe, and environmental metabolites. Advances in analytical instrumentation, such as mass spectrometers, and both experimental as well as computational methods to analyze data, coupled with the use of model organisms, have enabled fundamental discoveries of mechanisms of small molecule-mediated host-microbe interactions. The focus of this review is to detail the approaches applied in the last decade to disentangle microbiome-derived NPs in human and murine model systems. Select recent findings from diverse biological ecosystems are discussed to inform relevant parallels and potential strategies for research in human health.