Recombinant IL-34 alleviates bacterial enteritis in Megalobrama amblycephala by strengthening the intestinal barrier

The potential role of interleukin-34 (IL-34), an important cytokine that regulates intestinal function in mammals, is currently being explored in the context of fish intestinal diseases. In this study, we assessed the preventive potential of recombinant Megalobrama amblycephala IL-34 (rMaIL-34) protein in bacterial enteritis. MaIL-34 exhibited conserved structural and evolutionary features with teleost IL-34 and was found to be involved in the intestinal immune response to Aeromonas hydrophila infection. Furthermore, treatment with rMaIL-34 significantly improved the survival rate of M. amblycephala following A. hydrophila infection and alleviated the symptoms of enteritis in these fish. In vivo, rMaIL-34 enhanced goblet cell proliferation and mucus layer tightness, thereby maintaining mucosal integrity following infection. Additionally, rMaIL-34 attenuated the decrease in ZO-1 expression and inhibited the increase in intestinal permeability caused by A. hydrophila, thereby reducing the concentrations of DAO and D-LAC in the plasma. Furthermore, rMaIL-34 suppressed oxidative stress, apoptosis, and inflammatory responses triggered by A. hydrophila, thereby strengthening the immune barrier. At the microbiological level, rMaIL-34 contributed to improved intestinal microbiota distribution and enhanced the functions of intestinal microbiota in terms of energy metabolism, antibiotic biosynthesis, and oxidative phosphorylation. This study reveals, for the first time, the multiple roles of fish IL-34 in resistance to bacterial enteritis and paves the way for the development of rMaIL-34 as an immunotherapy for bacterial enteritis in fish.