Dietary mannan oligosaccharide effectively alleviates the lung and intestinal damages in the SIV-infected piglets caused by AFB1.

Aflatoxin B1 (AFB1) at low concentrations can enhance the replication and pathogenicity of swine influenza virus (SIV). Mannan oligosaccharide (MOS), a functional feed additive known to modulate intestinal microbiota and support immune homeostasis, may offer protective effects against such combined insults. This study investigated whether dietary MOS mitigates lung and intestinal damage in SIV-infected piglets exposed to AFB1 and explored the underlying mechanisms. Thirty-two piglets were randomly assigned to Blank, SIV, SIV + AFB1, and SIV + AFB1 + MOS (1000 mg/kg) groups for 2 weeks. MOS supplementation significantly reduced pulmonary SIV replication, indicated by lower M mRNA and NP protein levels, and improved weight loss and lung lesions. It also restored immune balance demonstrated by decreasing IL-6 and TNF-α and increasing IL-10 and TGF-β in the lungs and spleen. In the intestine, MOS increased beneficial Lactobacillus, reduced pathogenic Clostridium, alleviated jejunal injury, and upregulated the tight-junction proteins Occludin and Claudin-1. Serum metabolomics identified 37 MOS-responsive metabolites, notably elevated serotonin (5-HT) and reduced norepinephrine, involving pathways such as cAMP signaling and purine metabolism. Microbiota-metabolite association analysis further showed that Prevotella abundance positively correlated with 5-HT and negatively with norepinephrine. Overall, supplementation of MOS could alleviate the lung and intestinal damages in the SIV-infected piglets caused by AFB1, and some metabolites including 5-HT as well as the balance of intestinal flora and immunity might be the key to affect the function of MOS, and providing a novel strategy for preventing and controlling virus-toxin co-pathogenesis.