β,β-Dimethylacrylshikonin Alleviates Zebrafish (Danio rerio) Soyasaponin-Induced Enteritis by Maintaining Intestinal Homeostasis and Improving Intestinal Immunity and Metabolism

Soyasaponin intolerance is common in ancient fish species, making them susceptible to enteritis caused by dietary soybean meal. β,β-Dimethylacrylshikonin is the key active monomer found in Lithospermum erythrorhizon and is known for its multiple pharmacological activities. However, its effect on soybean meal-induced enteritis remains unknown. The administration of 2 g/kg of β,β-Dimethylacrylshikonin (LE) effectively alleviated 5 g/kg of soyasaponin-induced histopathological changes and dysfunction, as evidenced by the expression of inflammation-related genes (il-1β, il-8, and il10). Regarding the gut microbiota composition, LE therapy decreased the population of inflammation-linked Proteobacteria and concurrently elevated the proportion of Fusobacteriota, effectively sustaining the balance of the zebrafish gut microbiota. Moreover, at the genus level, LE treatment also increased the abundance of Cetobacterium. Transcriptional results suggested that LE intervention mainly regulated immune-related pathways, including cytokine–cytokine receptor interaction, the TGF-beta signaling pathway, taurine and hypotaurine metabolism, and arachidonic acid metabolism. In conclusion, 5 g/kg of soyasaponins caused intestinal injury in zebrafish, and β,β-Dimethylacrylshikonin can reduce intestinal inflammation by regulating the intestinal microbial balance and metabolic disorder, with the best effect at 2 g/kg.