Radiation-induced gut microbiota dysbiosis and Treg cells dysfunction: Mechanistic insights and clinical implications - A review

Regulatory T cells (T_regs) play a crucial role in maintaining immune balance. These cells primarily reside in the gut and exhibit properties of gut homing and polarization. The intestinal microenvironment, influenced by cytokines such as IL-1β, TGF-β and IL-10, significantly affects T_reg function. Intestinal T_regs regulate the function and renewal of intestinal epithelial cells while suppressing excessive immune responses. However, T_regs are plastic cells; during inflammatory conditions, although they accumulate in the gut, they may lose their suppressive capacity (termed ‘T_reg wannabes’) and potentially transform into pro-inflammatory cells. Dysbiosis of the gut microbiota is a significant driver of this phenomenon. Ionizing radiation not only creates an inflammatory microenvironment characterized by a cytokine storm but also induces dysbiosis of the gut microbiota. Through these mechanisms, T_regs can facilitate recovery from inflammation in the irradiated intestine by modulating the gut microbiota. This review examines the development of T_regs in the intestine, their proliferation in response to radiation, the loss of their suppressive ability, and the progression of radiation-induced intestinal injury (RIII) following dysbiosis treatment.