Disruption of endogenous polyamine metabolism affects colonic epithelium cell lineages

Polyamine homeostasis is essential for maintaining proliferation, differentiation, and stress responses in cells. However, its role in the biology of colonic epithelium remains poorly defined. We hypothesize that disrupting polyamine metabolism alters colonic epithelial lineage dynamics. Uranium Bearing Dust (UBD) is an environmental toxicant that alters gut homeostasis and epithelial cell lineage commitment, though the mechanism is not yet understood. Single cell RNA-sequencing of human colonic organoids exposed to UBD showed changes in the expression of transcripts involved in polyamine metabolism. Colonic organoids were exposed to UBD, polyamine synthesis inhibitor DFMO, or the polyamine catabolism inducer DENSPM. RT-qPCR was used to quantify changes in core metabolic genes (ODC1, SAT1, SMOX) and regulatory components of the endogenous polyamine control axis, including OAZ1, OAZ2, AZIN1, and AZIN2. Immunofluorescence microscopy was performed to assess proliferation and epithelial lineage populations. UBD, DFMO, and DENSPM treated colonoids showed cyclical and significant shifts in polyamine metabolism. Early time points showed polyamine synthesis alteration (ODC), followed by later changes in catabolic gene expression (SAT1, SMOX). Endogenous regulatory genes (OAZ1, OAZ2, AZIN1, AZIN2) also responded dynamically, potentially indicating a compensatory mechanism to rebalance intracellular polyamine levels. Immunofluorescence microscopy results revealed that disrupting polyamine metabolism leads to a significant expansion of enteroendocrine cells. These findings demonstrate that polyamine metabolism plays a critical role in colonic epithelium cell differentiation. Notably, UBD exposure significantly disrupts polyamine metabolism and shifts epithelial differentiation towards secretory cells, suggesting a potential link between environmental toxicant exposure and polyamine metabolism in gut epithelium homeostasis. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.