Microplastics induce liver inflammation in cattle through the rumen microbiota-gut-liver axis

BACKGROUND: Microplastics (MP) pollution is widespread in livestock farming environments. Exposure to MP can impair the gastrointestinal barrier, alter the structure and metabolism of the microbiota, and subsequently lead to organ damage. MP not only hinder cattle farming but also enter the food chain, posing a potential risk. Polyethylene (PE), a type of MP commonly detected in ruminant feed, has not yet been studied for its specific effects on cattle. Using calves as an animal model, this study investigates how exposure to MP induces toxicity via the rumen microbiota-gut-liver axis. RESULTS: Exposure to MP impaired weight gain and liver development in cattle, altered liver tissue pathology, increased blood lipopolysaccharide (LPS) levels, and triggered a systemic inflammatory response, identifying the liver as the primary target organ. Inflammation was closely associated with the dysbiosis of rumen microbiota and metabolites. MP exposure also damages the barrier integrity of the rumen, jejunum, and colon. The underlying mechanism involves MP altering the rumen microbial composition, which in turn triggers metabolic disorders, activates LPS synthesis pathways, and inhibits tight junction protein expression in the jejunum and colon. Although MP do not cause significant architectural damage to muscle tissue, they disrupt lipid homeostasis and nutrient composition, thereby promoting the deposition of pro-inflammatory LPS within muscle tissue. Rumen fluid metabolomics analysis revealed that differential metabolites were mainly enriched in the ATP-binding cassette transporter (ABC) pathway, with 4-fluoro-3-phenoxybenzoic acid and isovalerylglutamic acid being significantly correlated with levels of LPS, IL-6, TNF-α, and IL-1β. Notably, the concurrent increase in TNF-α and LPS in both the bloodstream and liver, alongside altered blood metabolomics, indicates that MP induce hepatic damage by disrupting the rumen microbiota-gut-liver axis. Transcriptomic analysis revealed that liver inflammatory injury was closely associated with NF-κB activation. Further mechanistic analysis supported the central role of the TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: MP impair liver function in cattle by disrupting the rumen microbiota-gut-liver axis. This process involves the perturbation of rumen flora and intestinal barriers, triggering LPS translocation into the bloodstream, and ultimately causing liver damage. Video Abstract.