Food‐Grade Chitosan‐Coated Nano Zero‐Valent Iron as a Functional Material for Gut–Liver Axis Regulation

ABSTRACT Environmental organic pollutants (EOPs) disturb host metabolism through direct toxicity and changes at the intestinal interface. This study evaluated chitosan‐coated nano zero‐valent iron (C‐nZVI) as a food‐grade, lumen‐active nano system for gut–liver axis regulation under contaminant exposure. Eighteen male C57BL/6J mice were assigned to control, EOP, and EOP + C‐nZVI groups ( n = 6 each). The EOP group received drinking water containing bisphenol A and PCB153 (50 μg/L each), whereas the EOP + C‐nZVI group received the same EOP exposure plus oral C‐nZVI (10 mg/kg) for 8 weeks. C‐nZVI was characterized by transmission electron microscopy, dynamic light scattering, polydispersity index, and zeta potential, and its functional relevance was interpreted through a food‐process‐engineering framework. EOP exposure increased body weight, liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic triglycerides (TGs), steatosis, and inflammatory cytokines ( p < 0.05), whereas the EOP + C‐nZVI group showed lower values for these pollutant‐associated readouts ( p < 0.05). EOP exposure altered gut microbiota structure (PERMANOVA R 2 = 0.286, p = 0.002), decreased Coprococcus , and increased Desulfovibrio ; the EOP + C‐nZVI group showed shifts in the opposite direction ( p < 0.05). Fecal butyrate and propionate were 52.90% and 40.00% higher, respectively, in the C‐nZVI group than in the EOP group ( p < 0.05). Coprococcus and butyrate were negatively correlated with hepatic injury markers (all r < −0.65, p < 0.01), whereas Desulfovibrio was positively correlated with these markers (all r > 0.58, p < 0.01). These findings are consistent with associations among C‐nZVI exposure, nano‐iron interfaces, microbial metabolism, and gut–liver axis responses; they do not establish mechanism or efficacy and require validation in larger, independent cohorts.