Understanding the Mechanistic Connection between Dysbiosis and Polyamine Regulation in Oral and Intestinal Inflammation- Role of Tregs and Th17 Cells.

Abstract

Periodontitis and inflammatory bowel disease (IBD) are chronic inflammatory conditions driven by dysbiotic microbial communities that subvert host mucosal immunity. Central to the immunopathology of both diseases is the disruption of the balance between regulatory T cells (Tregs) and T helper 17 (Th17) cells, an equilibrium that governs tissue homeostasis versus inflammatory destruction. Polyamines, principally putrescine (PUT), spermidine (SPD), and spermine (SPN), are emerging as critical immunometabolic regulators that modulate the plasticity and functional identity of both cell populations. Dysbiosis, particularly the enrichment of microbial communities that drive aberrant polyamine biosynthesis through ornithine decarboxylase (ODC)-dependent pathways, generates a polyamine-rich microenvironment that further dysregulates T cell function and promotes sustained inflammation. Experimental evidence demonstrates that mucosal polyamine levels correlate with dysbiosis, dysfunctional Treg (TregDys) expansion, and CD4⁺CD4⁺T cell hyperactivation, collectively contributing to and perpetuating chronic inflammation. The striking parallels between periodontitis and IBD reinforce the existence of conserved mechanisms linking mucosal dysbiosis to polyamine-driven immune dysregulation, with shared therapeutic implications for targeting the dysbiosis-T cell-polyamine axis to restore immune homeostasis. This review presents a unified mechanistic framework connecting oral and intestinal dysbiosis, polyamine dysregulation, and disruption of the Treg/Th17 balance, linking both diseases along the oral-gut axis.