Xylo-Oligosaccharides Attenuate T-2 Toxin-Induced Pulmonary Fibrosis by Inhibiting Intestinal Overgrowth and Gut-to-Lung Translocation of Staphylococcus saprophyticus

T-2 toxin, a widespread mycotoxin frequently detected in food and feed, severely threatens public health and livestock breeding safety. Although reports indicate its potential to cause pulmonary injury, the underlying mechanisms remain unclear. Here, we demonstrated that T-2 toxin compromised intestinal barrier integrity and increased abundance of S. saprophyticus in both the ileum and the lungs, thereby triggering pulmonary inflammation and fibrosis in piglets and mice. Transplantation of fecal microbiota from T-2 toxin-exposed piglets into recipient piglets mimicked the phenomena. NOD2 gene knockdown in mice reversed S. saprophyticus-induced pulmonary damage. Besides, xylo-oligosaccharides (XOS) inhibited the proliferation of S. saprophyticus driven by T-2 toxin and its translocation from the ileum to the lungs, thereby suppressing the NOD2/NF-κB signaling pathway and ultimately alleviating pulmonary fibrosis. This study deciphers the pivotal role of S. saprophyticus in mycotoxin-induced pulmonary fibrosis, highlighting the gut microbiota as a therapeutic target for preventing and treating mycotoxin-induced lung injury.