Probiotic intervention mitigates radiation-induced intestinal injury by alleviating oxidative stress in a human gut-on-a-chip.

Gastrointestinal acute radiation syndrome (GI-ARS) poses a critical public health concern, necessitating the development of effective medical countermeasures (MCM). Here, we evaluated the therapeutic potential of a commercially available probiotic formulation using a human gut-on-a-chip model that mimics the physiodynamic intestinal microenvironment. Intestinal epithelial Caco-2 cells were subjected to 8 Gy gamma radiation, targeting the epithelial layer, the culture medium, or both. The irradiated epithelial cells challenged to the irradiated medium resulted in significant DNA damage quantified by the presence of 53BP1 foci, increased cellular injury, and disrupted epithelial morphology. While epithelial irradiation alone did not compromise structural integrity, longitudinal exposure to irradiated medium induced oxidative stress, leading to morphological damage. Administration of the probiotic formulation significantly suppressed reactive oxygen species production, reduced epithelial damage, and preserved microarchitecture, independent of direct modulation of DNA damage. These findings suggest that probiotics may serve as a promising live biotherapeutic MCM for mitigating GI-ARS in high-risk radiological exposures.