Exposure to the growth promoter tylosin elicits gut microbiota disruption and metabolic imbalance in mouse model

Abstract

The environmental risk associated with the usage of the antibiotic tylosin as an animal growth promoter (AGPs) needs to be assessed because such agents are used in abundance and contamination of the environment is common, yet their effects on the physiology and gut microbiota composition of animals and humans are poorly understood. In this work, we performed metagenomic analysis and revealed that tylosin significantly disrupted the gut microbiota structure of animals, reduced species diversity, and caused the increase in the relative abundance of Blautia (60.95%). Enrichment of multiple contigs containing ARGs was observed, indicating that tylosin promotes antimicrobial resistance (AMR) development. Transcriptomic analyses of ileum tissues revealed perturbation in gene expression patterns suggestive of mitochondrial dysfunction and energy metabolism imbalance. These alterations might compromise nutrient absorption and utilization in the GI tract, and heighten the risk of development of obesity and non-alcoholic fatty liver disease (NAFLD). Furthermore, downregulation of immune-related gene expression was observed, indicating that tylosin caused immunosuppression and increased susceptibility to microbial infections when used over extended periods. Integrated omics analysis of the liver also showed significant disturbances in metabolism through activation of the arachidonic acid metabolism pathway, exacerbating inflammatory responses, and precipitating the occurrence of metabolic disorders such as type 2 diabetes mellitus (T2DM) and NAFLD. Our findings unveil the detrimental effects of tylosin on animal gut microbiota and metabolic functions and highlight the potential health risks to wildlife and humans when released into the environment. These findings highlight a need for cautious use of AGPs and the development of safer alternatives. Graphical abstract: [Figure not available: see fulltext.]