Harnessing Probiotics to Combat Nonylphenol Toxicity: A Multi-Omics Approach of Gut Microbiome Remodeling in Silurus meridionalis

Background As a ubiquitous environmental endocrine disruptor, nonylphenol (NP) threatens aquatic organisms, driving the need for sustainable mitigation strategies. While probiotics represent promising eco-friendly supplements, their molecular mechanisms against NP toxicity remain unclear. In this study, Silurus meridionalis received a 7-week probiotics ( Bacillus subtilis and Lactobacillus acidophilus ) pretreatment followed by 15-day NP exposure. Integrated metagenomics, transcriptomics, and metabolomics analysis, with qPCR and ELISA validation, to uncover microbial, gene and metabolic responses. Growth performance (SGR, WGR) was concurrently assessed. Result NP exposure significant suppressed WGR and SGR, and induced gut microbiota dysbiosis alongside lipid metabolism disorders in S.meridionalis . Probiotics pretreatment effectively reversed these toxic effects and restored the inhibited WGR and SGR. Multi-omics integration showed that probiotics protection was mediated via a coherent "microbe-host" co-metabolism network across three progressive layers: (1)Microbial Remodeling: enriching beneficial taxa (e.g., Bacteroides eggerthii and Cetobacterium sp.) and enhancing their functional capacity for short-chain fatty acid(SCFAs) synthesis and ethanolamine metabolism; (2) Host Gene Regulation: upregulating key lipid metabolism genes ( ek1 , cept1 , ept1 , mogat2 , abcg2a ) and restoring lipase activity; (3) Metabolic Pathways Activation and Physiological Repair: reactivating the NP‑suppressed Kennedy pathway, thereby promoting critical phospholipid (PE and PC) synthesis and ultimately restoring gut barrier function. These results were further were corroborated by qPCR and ELISA. Conclusion This study systematically elucidates that the probiotics alleviate NP toxicity by remodeling a "microbiota-host Kennedy pathway genes-metabolites (PE and PC)-growth performance" regulatory network. The key mechanism is the beneficial microbiota activating the host Kennedy pathway, restoring gut phospholipid homeostasis and barrier function. These findings provide a theoretical basis for developing targeted, lipid metabolism focused probiotic feed additives in sustainable aquaculture.