Metabolic modulation by antibiotic levofloxacin alters Cis-bifenthrin-induced neurotoxicity in amphibian tadpoles

Synthetic pyrethroids (SPs) and fluoroquinolones (FQs) are widely detected in aquatic environments and food chains, raising growing concern over their combined toxicity. However, the interaction between antibiotics and pesticides, particularly through host metabolism and microbiota, remains poorly understood. In this study, we investigated how the antibiotic levofloxacin (LEV) modulates cis-bifenthrin (cis-BF)-induced neurotoxicity in Xenopus laevis tadpoles. A 21-day co-exposure significantly impaired growth and locomotor behavior. Brain metabolomics revealed depletion of neuroprotective lipids (FAHFAs, PUFAs) and accumulation of potentially harmful organic acids and heterocycles. Transcriptomic analysis showed dysregulation of lipid metabolism, inflammation, and amino acid pathways. Given that LEV is a broad-spectrum antibiotic known to perturb gut microbiota composition, we speculated that its protective effects against cis-BF-induced neurotoxicity might involve modulation of the microbiota-gut-brain axis. Based on biochemical assays of intestinal tissues, LEV was found to mitigate cis-BF-induced oxidative stress and intestinal inflammation. However, 16S rRNA sequencing demonstrated microbiota alterations affecting SCFA- and amino acid- producing genera. Functional microbial shifts paralleled changes in brain metabolites, suggesting a microbiota-metabolism-neurotoxicity axis. This study demonstrates that although antibiotics can alleviate pesticide-induced intestinal inflammation, they concurrently exacerbate neurotoxicity, as evidenced by significant alterations in brain metabolites, transcriptomic profiles, and neurotransmitter levels. These findings highlight the complexity of microbial-metabolic interactions in environmental toxicology and the need for further investigation into their causal roles.