Antibiotics used as growth promoters in livestock and animal husbandry can be detected in animal-derived food. Epidemiological studies have indicated that exposure to these
antibiotic residues in food may be associated with
childhood obesity. Herein, the effect of exposure to a residual dose of
tylosin-an
antibiotic growth promoter-on host metabolism and gut microbiota was explored in vivo. Theoretical maximal daily intake (TMDI) doses of
tylosin were found to facilitate high-fat-diet-induced
obesity, induce
insulin resistance, and perturb gut microbiota composition in mice. The
obesity-related phenotypes were transferrable to germfree recipient mice, indicating that the effects of a TMDI dose of
tylosin on
obesity and
insulin resistance occurred mainly via alteration of the gut microbiota.
Tylosin TMDI exposure restricted to early life, the critical period of gut microbiota development, altered the abundance of specific bacteria related to host metabolic homeostasis later in life. Moreover, early-life exposure to
tylosin TMDI doses was sufficient to modify the ratio of primary to secondary
bile acids, thereby inducing lasting metabolic consequences via the downstream FGF15 signaling pathway. Altogether, these findings demonstrate that exposure to very low doses of
antibiotic residues, whether continuously or in early life, could exert long-lasting effects on host metabolism by altering the gut microbiota and its metabolites. IMPORTANCE This study demonstrates that even with limited exposure in early life, a residual dose of
tylosin might cause long-lasting metabolic disturbances by altering the gut microbiota and its metabolites. Our findings reveal that the gut microbiota is susceptible to previously ignored environmental factors.