Multi-Omics Analysis Uncovers Acute Hypoxia-Induced Gut Damage and the Underlying Protective Mechanisms of Probiotic Clostridium butyricum B3 in Yellow Catfish (Pelteobagrus fulvidraco).

Acute hypoxia stress poses a significant challenge in aquaculture, not only compromising gut health but also resulting in substantial economic losses. Using an integrated multi-omics approach, this study demonstrates that hypoxia severely disrupts the intestinal function of yellow catfish (Pelteobagrus fulvidraco), specifically manifesting as phospholipid metabolism disorders, inhibited fatty acid β-oxidation, reduced short-chain fatty acid (SCFA) synthesis, imbalanced gut microbiota (e.g., decreased levels of beneficial lactic acid bacteria Lactococcus and Clostridium sensu stricto 1), and downregulation of detoxification pathways mediated by cytochrome P450. Building upon the previously isolated and identified high-yield SCFA-producing probiotic Clostridium butyricum B3 from yellow catfish in early work, this research further investigated the efficacy and mechanisms of B3 supplementation in mitigating hypoxia-induced intestinal barrier damage in yellow catfish. The results indicated that the supplementation of C. butyricum B3, particularly at a dose of 3.0 × 10⁷ CFU/g, significantly reduced histological damage, enhanced the expression of key tight junction proteins (such as ZO-1 and Claudin), and modulated hypoxia-inducible factor signaling pathways (including HIF-1α, FIH, and PHD). Furthermore, the application of C. butyricum B3 restored microbial ecological balance by promoting the growth of beneficial bacteria like Cetobacterium and inhibiting potential pathogens such as Acinetobacter. In conclusion, these findings underscore the potential of C. butyricum B3 as a novel probiotic strategy for enhancing fish hypoxia tolerance and maintaining intestinal integrity, offering valuable insights for sustainable aquaculture practices.