Deoxynivalenol-induced intestinal toxicity in piglets is mediated by multi-kingdom microbial dysbiosis and metatranscriptomic reprogramming

Mycotoxin contamination of feed and food, particularly with deoxynivalenol (DON), poses significant threats to intestinal health in livestock, yet the role of gut fungi (mycobiota) and fungal-bacterial interactions remains unclear. Across four piglet experiments integrating multi-omics and network analyses, we found that DON selectively disrupts the gut mycobiota, depleting the dominant yeast Kazachstania slooffiae and inducing a modular, competitive cross-kingdom network, while bacterial diversity remains intact. In contrast, AFB 1 did not alter fungal composition, likely due to the immature mycobiota of suckling piglets, whereas antibiotic-associated diarrhea (AAD) caused bacterial collapse and a hyper-connected fungal network. Metatranscriptomics revealed that DON reprograms microbial activity toward virulence and detoxification at the expense of anaerobic metabolism, with coordinated downregulation of the microbial porA transcript (encoding pyruvate ferredoxin oxidoreductase) in Clostridium polysaccharolyticum and Methanobrevibacter , and suppression of butanoate metabolism and methanogenesis, supported by in silico predictions of direct DON-PFOR interaction. These transcriptional changes translated into reduced colonic butyrate and total short-chain fatty acids. Together, our findings establish a multi-kingdom framework for mycotoxin toxicity, positioning the mycobiota, particularly K. slooffiae and porA , as key ecological and molecular nodes linking dysbiosis to functional impairment with implications for mitigating DON-induced losses in livestock and improving global food safety.