Emerging chemophysiological diversity of gut microbiota metabolites.

Tryptophan metabolites exhibit chemical diversity and engage multiple receptors, resulting in pleiotropic effects that modulate tumor development, therapeutic response, host defense against pathogens, regulation of metabolic syndrome, and potential correlations with neurological disorders. Bile acids, synthesized in the liver and modified by gut microbiota, exhibit structural and functional diversity, and play vital roles in immunomodulation, gut–liver signaling, energy metabolism, disease progression, and treatment. Despite advances in microbiome studies, comprehending the complex network of host–microbe molecular interactions remains challenging. Emerging techniques – such as stable isotope tracing, high-throughput microbial culturomics, metabolomics, chemical genetic screens, and chemoproteomics – are essential for deeper insights. With a better understanding of host–microbe interaction mechanisms, exploiting the chemophysiology of microbiota metabolites offers significant therapeutic potential, including the development of small-molecule inhibitors and engineered probiotics. Human physiology is profoundly influenced by the gut microbiota, which generates a wide array of metabolites. These microbiota-derived compounds serve as signaling molecules, interacting with various cellular targets in the gastrointestinal tract and distant organs, thereby impacting our immune, metabolic, and neurobehavioral systems. Recent advancements have unveiled unique physiological functions of diverse metabolites derived from tryptophan (Trp) and bile acids (BAs). This review highlights the emerging chemophysiological diversity of these metabolites and discusses the role of chemical and biological tools in analyzing and therapeutically manipulating microbial metabolism and host targets, with the aim of bridging the chemical diversity with physiological complexity in host–microbe molecular interactions. [ABSTRACT FROM AUTHOR]