Polystyrene microplastics-induced gut–liver axis injury in mice: Protective effect and mechanisms of sodium humate

Microplastics (MPs), as widespread and increasingly prevalent environmental pollutants, pose a persistent threat to aquatic organisms and mammals, including humans. Sodium humate (HNa), a naturally derived humate salt that is widely available, low-cost, and has a favorable safety profile, exhibits multiple biological activities, including antimicrobial, anti-inflammatory, and antioxidant properties. This study was designed to evaluate whether HNa could protect against intestinal and hepatic injury caused by polystyrene microplastics (PS-MPs) exposure in mice and to clarify the involvement of the gut-liver axis. HNa intervention alleviated impairment of body weight gain and colonic pathological injury following PS-MPs exposure. HNa enhanced intestinal antioxidant capacity, suppressed pro-inflammatory mediator expression, and promoted anti-inflammatory factor expression. Furthermore, HNa upregulated the expression of mucins and adherens junction and tight junction proteins, thereby restoring intestinal barrier function and limiting endotoxin translocation. In the liver, HNa ameliorated histopathological lesions, improved biochemical injury markers, attenuated inflammatory responses, and suppressed excessive activation of the TLR4/NF-κB pathway. Collectively, HNa mitigated gut-liver axis injury following PS-MPs exposure in mice through coordinated protection of intestinal barrier integrity and attenuation of hepatic inflammatory signaling. This study provides the first experimental evidence that HNa mitigates PS-MPs toxicity by protecting the gut-liver axis, supporting its potential as a practical intervention strategy against MPs-related digestive system injury.