Neurotoxic effects of Cis-bifenthrin on microbe-gut-brain axis: Disruption of neurolipid balance in Xenopus laevis

The neurotoxic effects of cis-bifenthrin (cis-BF) on amphibians and its molecular mechanisms are unclear despite its common presence in aquatic environments. In present study, female Xenopus laevis were subjected to a three-month treatment with environmentally relevant concentrations of 60 and 300 ng/L cis-BF. Metabolomic analysis of brain tissue revealed differential metabolites enriching bile acid (BA) synthesis, impacting β-amyloid protein deposition. Reduced polyunsaturated fatty acids (PUFAs), essential for membrane integrity, were observed. Elevated amyloid β-protein and lipopolysaccharide (LPS) levels suggested potential Alzheimer's-like symptoms induced by cis-BF. Given PUFAs and BAs are processed via enterohepatic circulation, a notable decrease in the abundance of genera linked to PUFAs and BAs metabolism was observed. Gut metabolomics revealed decreased concentrations of PUFAs and secondary BAs across cis-BF treatment groups, attributed to changes in associated microbial communities. Cis-BF exposure raised intestinal LPS levels and plasma proinflammatory cytokines, resulting in intestinal damage. This facilitated the entry of LPS into the bloodstream and brain tissue, indicating a cytokine-LPS interaction that promotes LPS transit to the brain through the bloodstream. Our study suggests that cis-BF-induced alterations in gut microbiota and metabolism may trigger Alzheimer's-related neurological disorders in Xenopus laevis via the gut-brain axis by inducing neurolipid disorder and inflammation.