Paracoccus marcusii IHA034 Protects Larimichthys polyactis Against Oxidized Fish Oil and H2O2-Induced Intestinal Injury: Divergent Keap-1/Nrf2 Responses In Vivo and In Vitro

Paracoccus marcusii is an astaxanthin-synthesizing bacterium with antioxidant potential, but its mechanisms mitigating intestinal oxidative injury in fish remain unclear. Herein, we explored the protective function of P. marcusii IHA034 (CGMCC No. 25301) in juvenile Larimichthys polyactis, combining an in vivo oxidized-fish-oil challenge model and an in vitro H2O2-stimulated primary intestinal cell model. A 51-day feeding trial showed that 1.0 g/kg dietary P. marcusii supplementation improved growth performance, enhanced intestinal antioxidant enzyme activities, and restored epithelial ultrastructural damage. A strikingly high relative abundance of Paracoccus (90.50%) was detected in the gut digesta of the PM1.0 group, accompanied by reduced microbial α-diversity. In vivo intestinal transcriptomics and qPCR showed downregulated nrf2 mRNA, alongside activated complement and anti-apoptotic responses. However, P. marcusii pigment-rich crude extracts activated the Keap-1/Nrf2 pathway and rescued H2O2-induced cell injury in vitro. These findings demonstrate multi-modal protective effects of P. marcusii IHA034 and uncover contrasting Keap-1/Nrf2 regulatory patterns between in vivo intestinal tissue and in vitro cell models, providing mechanistic support for the application of this astaxanthin-producing bacterial resource in aquaculture.