Lincomycin as a growth-promoting antibiotic induces metabolic and immune dysregulation in animals

Since animal growth promoters (AGPs) are used in large quantities and commonly released to the environment from animal farms, it is necessary to determine whether such agents should be regarded as an environmental toxin that poses a threat to the ecosystem and health risk to wildlife. In this study, a multi-omics approach was employed to explore the effects of a representative AGP, lincomycin, on key metabolic and physiological functions of animals, using a mouse model. The results indicated that exposure to lincomycin resulted in a significant increase in growth rate of mice (50.11 %) over an 8 weeks period, during which significant decrease (61.94 %) and increase (68.64 %) in the relative abundance of Firmicutes and Escherichia coli, respectively, was observed in the gut microbiota, indicating that the gut microbiota structure has been altered. Moreover, the mice exhibited altered lipid profiles and liver damage suggestive of early-stage non-alcoholic fatty liver disease (NAFLD). Disruptions in blood glucose and insulin levels associated with type 2 diabetes mellitus (T2DM) were also observed. Furthermore, lincomycin was found to cause suppression in inflammatory responses, as evidenced by the downregulation of related genes and elevated inflammatory mediators, potentially resulting in increased susceptibility to microbial infection. Our findings underscore the detrimental effects of lincomycin on animal health and highlight the necessity for comprehensive toxicological assessments of lincomycin and other AGPs before their environmental release.