Investigating the Regulation of Polyamine Metabolism during Gastrointestinal Infection and its Impact on Inflammation and Carcinogenesis

Abstract

Recent advances in understanding polyamine metabolism have highlighted its importance in inflammation and cancer development. Polyamines, including putrescence, spermidine, and spermine, play crucial roles in cellular growth and survival. Herein, we show that spermine oxidase (SMOX) deletion protects against Helicobacter pylori-induced gastric cancer progression. We implicate the highly reactive aldehyde acrolein, a byproduct of SMOX activity, in inducing DNA damage and contributing to cancer progression. Additionally, spermidine’s role in protein modification through the hypusination pathway highlights its importance in regulating cellular functions as inhibition of this pathway chemically or genetically leads to alterations in translation and procarcinogenic pathways. Aconitate decarboxylase 1, which is involved in innate immunity, is a target of the hypusination pathway and we show that it can modulate inflammation and colitis through the regulation of the gut metabolome and microbiome. Together these findings suggest that regulating polyamine metabolism and related enzymes is critical during inflammation and carcinogenesis.