Dietary Butyrate as a Functional Feed Additive in Aquaculture: A Systematic Review and Meta-Analysis of Immunological and Antioxidant Responses With Dose-Response Insights

Aquaculture intensification has increased the demand for nutritional strategies that support immune responses and oxidative balance in cultured finfish and crustaceans, thereby reducing disease susceptibility and improving production stability. Butyrate, a short-chain fatty acid increasingly incorporated into aquafeeds as a functional feed additive, has shown promise in enhancing immune responses and antioxidant defenses, but reported effects vary widely across species, life stages, and supplementation levels. This systematic review and meta-analysis synthesizes findings from 65 studies (1174 dose-control comparisons) across 23 aquaculture species to assess butyrate's effects on innate and adaptive immunity, oxidative stress, and antioxidant capacity. Dietary butyrate generally enhanced innate immune responses (g = 2.14, 95% CI: 1.66-2.63) and antioxidant enzyme activity (g = 1.59, 95% CI: 1.07-2.12), increased IL-10 (g = 0.64), and reduced MDA (g = -1.36). Effects on adaptive immunity were positive but more heterogeneous among studies (g = 0.98, 95% CI: 0.33-1.63), and pooled effects on pro-inflammatory cytokines, chemotactic cytokines, and immune signaling pathways were not significant. Trim-and-fill adjustment attenuated the pooled estimates for innate immunity (g = 1.33) and antioxidant enzymes (g = 0.84), indicating possible small-study effects. In dose-response meta-regression, dietary inclusion level explained little of the heterogeneity (pseudo-R 2 ≤6.3%), and no inclusion range was consistently associated with stronger responses. These findings support butyrate as a promising functional feed additive, while indicating that dose recommendations require species-specific dose-response trials.