Fish gut barrier damage under intensive culture model is a significant concern for aquaculture industry. This study aimed to investigate the effects of bile acids (BAs) on gut barriers in Micropterus salmoides. A germ-free (GF) zebrafish model was employed to elucidate the effects of the direct stimulation of BAs and the indirect regulations mediated by the gut microbiota on gut barrier functions. Four diets were formulated with BAs supplemented at 0, 150, 300 and 450 mg/kg, and these 4 diets were defined as control, BA150, BA300 and BA450, respectively. After 5 weeks of feeding experiment, the survival rate of fish fed with BA300 diet was increased (P < 0.05). Histological analysis revealed an improvement of gut structural integrity in the BA150 and BA300 groups. Compared with the control group, the expression of genes related to chemical barrier (mucin, lysozyme and complement 1) and physical barrier (occludin and claudin-4) was increased in the BA150 and BA300 groups (P < 0.05), and the expression of genes related to immunological barrier (interleukin [IL]-6, tumor growth factor β, IL-10, macrophage galactose-type lectin and immunoglobulin M [IgM]) was significantly increased in the BA300 group (P < 0.05), but the expression of genes related to chemical barrier (hepcidin) and immunological barrier (IL-1β, tumor necrosis factor-α, IL-6 and arginase) was significantly decreased in the BA450 group (P < 0.05). Gut microbiota composition analysis revealed that the abundance of Firmicutes was augmented prominently in the BA150 and BA300 groups (P < 0.05), while that of Actinobacteriota and Proteobacteria showed a downward trend in the BA150 and BA300 groups (P > 0.05). The results of the gut microbiota transferring experiment demonstrated an upregulation of gut barrier-related genes, including immunoglobulin Z/T (IgZ/T), IL-6, IL-1β and IL-10, by the gut microbiota transferred from the BA300 group compared with the control (P < 0.05). Feeding the BA300 diet directly to GF zebrafish resulted in enhanced expression of IgM, IgZ/T, lysozyme, occludin-2, IL-6 and IL-10 (P < 0.05). In conclusion, BAs can improve the gut barriers of fish through both direct and indirect effects mediated by the gut microbiota.

集约化养殖模式下鱼肠屏障的损伤是水产养殖业关注的一个重要问题。本研究旨在研究胆汁酸 (BAs) 对鲑鱼肠道屏障的影响。采用无菌 (GF) 斑马鱼模型来阐明 BA 的直接刺激和肠道微生物群介导的间接调节对肠道屏障功能的影响。以 0、150、300 和 450 mg/kg 的 BA 配制四种日粮，这 4 种日粮分别定义为对照、BA150、BA300 和 BA450。饲养试验5周后，饲喂BA300日粮的鱼存活率提高（P < 0.05)。组织学分析显示 BA150 和 BA300 组的肠道结构完整性有所改善。与对照组相比，BA150 和 BA300 组化学屏障相关基因（粘蛋白、溶菌酶和补体 1）和物理屏障相关基因（occludin 和 claudin-4）表达增加（ P < 0.05）， 且免疫屏障相关基因（白细胞介素[ IL ]-6、肿瘤生长因子β、IL-10、巨噬细胞半乳糖型凝集素、免疫球蛋白M[ IgM ]）在BA300组显着升高（P  < 0.05），但表达与化学屏障（hepcidin）和免疫屏障（IL-1β，肿瘤坏死因子）相关的基因-α、IL-6和精氨酸酶）在 BA450 组显着降低（P  < 0.05）。肠道菌群组成分析显示，厚壁菌门丰度在 BA150 和 BA300 组显着增加（P  < 0.05），而放线菌门和变形菌门丰度在 BA150 和 BA300 组呈下降趋势（P  > 0.05）。肠道微生物群转移实验的结果表明，从 BA300 组转移的肠道微生物群会上调肠道屏障相关基因，包括免疫球蛋白 Z/T ( IgZ/T )、IL-6、IL-1β和IL-10与对照相比（P < 0.05)。将 BA300 饲料直接喂给 GF 斑马鱼导致IgM、IgZ/T、溶菌酶、occludin-2、IL-6和IL-10的表达增强（P  < 0.05）。总之，BA 可以通过肠道微生物群介导的直接和间接作用改善鱼类的肠道屏障。