Supplementation and Elimination of Microbiome‐Produced Metabolites in the Treatment of Human Disease

The human gut microbiome has a complex and influential relationship with host physiology that is governed through commensal-derived metabolites, small molecules, and endogenous microbial patterns. Indeed, microbial metabolites from the gut microbiome have been implicated in promoting health as well as contributing to the pathogenesis of microbiome-associated diseases. Live microbial therapeutics, such as probiotics and fecal microbiota transplantations, have been extensively utilized to establish health-promoting assemblages of bacteria and their associated beneficial metabolites. However, broad clinical use of live microbial therapeutics is limited by efficacy, specificity, and safety concerns. To circumvent this, a postbiotic approach can be taken, in which a beneficial effect may be achieved by direct administration of bacterially derived bioactive molecules. Alternatively, in cases where microbiome-derived metabolites drive disease, specific oral inhibitors can be used to restrict compound production. In this review, we examine the use of postbiotics to alleviate disease and highlight recent translational successes. Additionally, we discuss emerging approaches for precision elimination of disease-causing metabolites, as well as the exciting possibility of utilizing bacteriophages to modulate the production of metabolites in the microbiome.