Taurine mitigates intestinal injury and spatial memory deficits induced by high-fat diet and abdominal irradiation.

Combined metabolic dysfunction and ionizing radiation produce multifactorial systemic harm, challenging organismal homeostasis and cognitive function. Here, we define a new role for dietary taurine (Tau) protection against combined high-fat diet (HFD) and whole-abdominal irradiation (WAI) stress. In a two-sex murine model, we show that Tau intervention blocks metabolic organ damage and severe structural enteropathy. Histological analyses indicate that Tau preserves the intestinal mucosal barrier, which is accompanied by the restoration of Mucin 2 (MUC2) expression. Furthermore, 16S rRNA sequencing showed that Tau reshapes gut dysbiosis, increasing the relative abundance of the mucin-degrading bacterium Akkermansia muciniphila, which may potentially contribute to mucosal homeostasis. Coincident with the stabilization of this mucin-microbiome interface, we observed that Tau attenuates systemic endotoxemia and reduces inflammatory extracellular vesicle transmission of the gut-brain axis. Consequently, this reduced peripheral inflammation preserves hippocampal dentate gyrus (DG) architecture and ameliorates spatial memory deficit. Importantly, while this microbiome-gut-brain protection is similar in both sexes, systemic immune responses are strikingly sexually dimorphic, mandating a sex-stratified therapeutic approach. Together, these studies reveal a potential microbiome-associated link in Tau-induced systemic resilience, providing a translatable nutritional strategy against combined radiotoxic and metabolic disorders.