Blocking TNFR1 internalization and cell death represents a critical mechanism for alleviating enteritis in adult grass carp: The potential role of dietary myo-inositol in enhancing intestinal health.

In high-density intensive aquaculture systems, enteritis has emerged as a critical health concern. In bony fish, the intestine serves as the core organ of the digestive system and plays an important part in maintaining physiological homeostasis. Disruption of intestinal barrier integrity can lead to metabolic disturbances, inflammatory responses, and progressive impairment of intestinal barrier function. Myo-inositol (MI), a vitamin-like nutrient, exerts notable beneficial effects on the structural integrity of physical barriers and non-specific immunity in various aquatic species. A total of 450 adult grass carp (Ctenopharyngodon idella) (704.84 ± 0.91 g) were randomly divided into 6 treatments (3 replicates per treatment) to receive six levels of dietary MI (35 [basal diet], 98, 195, 292, 389, and 487 mg/kg). Following an 8-week feeding period, intestinal inflammation was induced using dextran sulfate sodium (DSS). Compared with the MI supplement group, the results demonstrated that MI deficiency (basal diet) suppressed intestinal development in adult grass carp, aggravated intestinal structural damage in DSS-induced enteritis, and reduced the number of intestinal goblet cells (P < 0.001). Moreover, MI deficiency increased the incidence of DSS-induced enteritis (P < 0.001). Mechanistically, MI deficiency caused sustained NF-κB p65 activation by disrupting early endosome formation and impairing TNFR1 internalization (P = 0.015). This cascade ultimately triggered cell apoptosis and exacerbated intestinal inflammation. Collectively, these findings revealed how MI contributes to the maintenance of intestinal barrier function and enhanced understanding of its role in regulating intestinal health in grass carp.