Mannan-oligosaccharide induces trained immunity activation and alleviates pathological liver injury in turbot (Scophthalmus maximus)

The liver is one of the principle immune organs in fish, and involves lots of physiological processes. Pathological liver injury is a common symptom in fish farming caused by bacterial infection. Mannan-oligosaccharide (MOS) has been considered as a promising diet additive in aquaculture due to its liver protection. However, the specific mechanism by which MOS protects fish from pathological liver injury remains unknown. In this study, we established a MOS intraperitoneal injection model in turbot (Scophthalmus maximus) and found that MOS-treated turbots exhibited a rapid and elevated inflammatory response during secondary bacterial infection. Besides, MOS treatment caused significant changes in metabolic signaling (such as glycolysis, glutamine metabolism, and fatty acid metabolism) and histone epigenetic modifications (including H3K4me1, H3K4me3 and H3K9me3), which are typical characteristics of trained immunity activation. Moreover, we found an enhanced capability for bacterial clearance in MOS-treated turbot, resulting alleviated phenotypes of liver injury and histopathology changes. Taken together, these findings suggest that MOS might be the inducers of trained immunity in teleost fish, which contributes to protecting turbot from liver injury.