Engineered S. cerevisiae-pYD1-ScFv-AFB1 mitigates aflatoxin B1 toxicity via bio-binding and intestinal microenvironment repair.

The highly toxic aflatoxin B1 (AFB1) is considered one of the primary risk factors for hepatocellular carcinoma, while effective measures after AFB1 exposure remain to be optimized. This study utilized cell-surface-display technique to construct an engineered S. cerevisiae-pYD1-ScFv-AFB1 (S.C-AF) that specifically binds AFB1, and verified the potential mechanism of S.C-AF in vivo through AFB1-induced (gastric perfused with 0.3 mg/kg/d AFB1 per day) liver injury mouse model. In this experiment, the C57BL/6 mouse model of AFB1-induced liver injury was treated with S.C (gastric perfused with 1 × 109 CFU/mL S.C per day) and S.C-AF (gastric perfused with 1 × 109 CFU/mL S.C-AF per day) for 4 weeks, respectively. With probiotic properties optimized, S.C.-AF achieved an in vitro AFB1 binding capacity 1.7 times higher than S. cerevisiae. Furthermore, S.C-AF could alleviate AFB1-induced liver injury by reducing proinflammatory cytokine secretion and apoptotic protein expression, enhancing antioxidative capacity via Nrf2 activation, and simultaneously reversing intestinal tight junction protein deficiency, increasing intestinal barrier permeability, and improving intestinal dysbiosis caused by AFB1 exposure. S.C-AF alleviates AFB1-induced liver lesions, which might be a novel intervention to mitigate aflatoxin toxicity.