Effects of Replacing Fishmeal with Soybean Meal on Intestinal Histology, Antioxidation, Endoplasmic Reticulum Stress, Inflammation, Tight Junction, and Microbiota in Olive Flounder (Paralichthys olivaceus)

A limited supply and price shortages of fishmeal with the expansion of aquaculture make it necessary to seek alternative protein sources. Soybean meal (SM) has been the widely preferred replacer for fishmeal in fish diets. Nevertheless, this substitution, especially when given at high doses, potentially shows adverse impact on fish intestinal health. This study aimed to investigate the effect of replacing fishmeal with SM on intestinal health in olive flounder (<i>Paralichthys olivaceus</i>). A 56-day feeding trial was conducted with 450 juvenile fish (initial weight: 6.32 ± 0.01 g) randomly allocated to five diets with graded SM replacement: 0% (FM), 12% (SM12), 24% (SM24), 36% (SM36), and 48% (SM48). The results demonstrated that concentrations of glucose, total triglyceride, and low-density lipoprotein cholesterol increased, whereas total protein and high-density lipoprotein cholesterol contents, and lysozyme activity decreased in serum with increasing dietary SM levels. Meanwhile, total antioxidant capacity and superoxide dismutase activity significantly decreased at replacement levels exceeding 24%, accompanied by elevated malondialdehyde concentration (<i>p</i> < 0.05). Compared with the FM group, the SM24, SM36, and SM48 groups showed significantly reduced VH and increased lamina propria width (<i>p</i> < 0.05). Increasing dietary SM levels upregulated expression of genes related to endoplasmic reticulum stress (ERS) (<i>chop</i>, <i>perk</i>, and <i>grp78</i>), inflammation (<i>tnf-α</i> and <i>il-6</i>), and apoptosis (<i>bax</i>, <i>casp3</i>, <i>casp6</i>, and <i>casp9</i>), while downregulated anti-inflammatory cytokines (<i>il-10</i> and <i>tgf-β1</i>) and tight junction-related genes (<i>zo-1</i>, <i>zo-2</i>, <i>claudin-5</i>, <i>ocln</i>, <i>muc-13</i>, and <i>muc-15</i>) in the intestine (<i>p</i> < 0.05). There were significant differences in the abundances of intestinal microbiota at both the phylum and genus levels among the FM, SM24, and SM36 groups (<i>p</i> < 0.05), but the clusters and microbiota composition of the SM24 group were more similar to those of the FM group. In conclusion, replacing 24% of fishmeal with SM induced intestinal dysfunction through evoking ERS, inflammation, barrier disruption, and microbial dysbiosis in olive flounder.