The liquid crystal monomer EtCBN induced neurotoxicity by activating the NOD-like receptor signaling pathway through the Muribaculum-epigallocatechin axis

Liquid crystal monomers (LCMs) demonstrate blood-brain barrier penetrability and exhibit progressive bioaccumulation in neural tissues, though their neurotoxic mechanisms remain incompletely characterized. Notably, EtCBN has been identified as the most abundant and the highest detection frequency in residential indoor dust in China. By establishing an 8-week EtCBN exposure model in mice (administered via oral gavage at 20/200 μg/kg), we demonstrated that environmentally relevant doses significantly impaired cognitive function. In vitro experiments further confirmed the direct toxicity of EtCBN to BEND3, BV2, and HT22 cells. Then, we integrated hippocampal transcriptomics, plasma metabolomics, gut microbiota 16S rRNA sequencing, and microbiota-derived metabolite profiling. The results revealed that EtCBN exposure caused dysregulation of intestinal flora, significantly reduced the abundance of Muribaculum, reshaped plasma metabolite profiles, and activated the NOD-like receptor signaling pathway, thereby causing neuroinflammation and ultimately impairing hippocampal synaptic plasticity. The Muribaculum-epigallocatechin axis mediated through bidirectional interactions played a pivotal role in this biological process. Notably, exogenous supplementation of nicotinamide adenine dinucleotide (NAD⁺) reversed cognitive impairment induced by EtCBN. This study provides the first systematic elucidation of the molecular mechanisms by which EtCBN impairs neural function via a Muribaculum-epigallocatechin axis-driven inflammatory signaling network, offering experimental evidence for assessing LCM-related health risks.