Canonical polyamines such as agmatine, putrescine, and spermidine are evolutionarily conserved metabolites found in nearly all forms of life ranging from bacteria to humans. Recently, interactions between polyamines produced by gut bacteria and human intestinal cells have been proposed to contribute to both Irritable Bowel Syndrome with Diarrhea (IBS-D) and inflammatory bowel diseases. However, the molecular mechanisms that underlie these effects are often unclear due in part to limitations in the methods used to manipulate and study polyamine functions