Sinomenine improves resistance to foodborne enteritis and Anti-bacteria mucosal immunity in grass carp

Based on our previous study in zebrafish, sinomenine was found to relieve foodborne enteritis through immunomodulation. To examine the protective effects of sinomenine on mucosal immunity in farmed fish species, a dietary inclusion study was conducted in grass carp juveniles by adding sinomenine to soybean meal feed. After a 5-week feeding trial to model foodborne enteritis, the gut and liver tissues were examined for histopathology, enteritis-related gene expression, transcriptome, and 16 s rRNA gene sequencing. The results demonstrated that including sinomenine in the diet at the concentration of 2 g/kg could prevent intestinal pathological changes, such as a decrease in the number of goblet cells and increased glycogen, induced by 40% soybean meal substitution. At the molecular level, the downregulated proinflammatory genes, together with upregulated anti-inflammatory genes (such as il10, il13, and tgfβ) were observed. At the omics level, for the DEGs, the downregulated intestinal pathway "phagosome" and term "platelet activation" indicated control of inflammation, while the upregulation of the "PPAR signaling pathway" in both the gut and liver, suggests enhanced immune homeostasis. For the mucosal surface in the sinomenine-supplemented group, we observed not only control of pathogenic Camparilobacterota and Aeromonas but also an increase in Actinobacteria, which may enhance mucosal immunity. Due to the influence of the gut-liver axis, hepatic metabolism was altered, particularly with an upregulation of "fatty acid degradation" and "tryptophan metabolism". Subsequently, the fish in the sinomenine group exhibited a significantly higher survival rate after a 7-day immersion challenge with Aeromonas hydrophila, with less inflammatory CD4 signals in the gills. Hepatic hypoxia and low respiratory efficiency in the gill may be a side effect. In summary, sinomenine demonstrated a protective effect on the mucosal immunity of the gut and gill, thereby preventing enteritis and subsequent bacteria challenges. Therefore, sinomenine could be employed in aquaculture as phytotherapy, at the very least through dietary supplementation in fish.