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Abstract Certain antimicrobial preservatives (APs) have been shown to perturb gut microbiota. So far, it is not yet fully known that whether similar effects are observable for a more diverse set of APs. It also remains elusive if biogenic APs are superior to synthetic APs in terms of safety. To help fill these knowledge gaps, the effects of eleven commonly used synthetic and biogenic APs on the gut microbiota and glucose metabolism were evaluated in the wild-type healthy mice. Here, we found that APs induced glucose intolerance and perturbed gut microbiota, irrespective of their origin. In addition, biogenic APs are not always safer than synthetic ones. The biogenic AP nisin unexpectedly induced the most significant effects, which might be partially mediated by glucagon-like peptide 1 related glucoregulatory hormones secretion perturbation.