Unlocking the Antioxidant Potential of Sea Cucumber Viscera: Pre-Treatment Modulates the Keap1-Nrf2 Pathway and Gut Microbiota to Attenuate Cold Stress-Induced Oxidative Damage

The internal organs of sea cucumbers (SCV) are a byproduct of the seafood processing industry and hold untapped potential as a functional food. This study investigates the antioxidant capacity of SCV and its regulatory effects on the gut microbiota in a mouse model of oxidative stress induced by chronic cold exposure. The results indicate that SCV possesses a rich nutritional composition, containing various components such as calcium, phosphorus, and polysaccharides, and exhibit strong scavenging activity against three types of free radicals in vitro: DPPH, OH^-, and O₂^-. SCV significantly reduced MDA levels in both serum and liver, while activating the Keap1-Nrf2/HO-1 pathway, leading to a significant decrease in the expression of HSP70 and HSP90 genes and a marked increase in Nrf2 gene expression, thereby alleviating oxidative damage. Histological analysis revealed that SCV alleviated liver damage, reducing hepatocellular vacuolization and inflammatory cell infiltration. Additionally, SCV modulated the diversity of the gut microbiota, increasing the abundance of <i>Allobaculum</i>, <i>Turicibacter</i>, <i>Bifidobacterium</i>, and <i>Akkermansia</i>, while enriching the synthesis pathway of vitamin B12 (PWY-7377). This study is the first to repurpose sea cucumber viscera waste into a functional food, demonstrating its dual mechanism of alleviating oxidative stress by activating the Keap1-Nrf2/HO-1 antioxidant pathway and regulating the gut microbiota. These findings offer an innovative strategy for the high-value utilization of agricultural by-products and the development of multifunctional health-promoting products.