Does Dietary Consumption of Antibiotics by Humans Promote Antibiotic Resistance in the Gut Microbiome?

Abstract

Mandated authorities have developed principles for evaluating the safety of antimicrobial residues in food and have established microbiological acceptable daily intakes (ADIs) and recommended maximum residue limits (MRLs) for antibiotic residues in food products. The evaluation of the ADI is based in relevant scientific information such as MIC data of predominant human intestinal bacteria. However, it does not include data derived from minimal selective concentration (MSC) predictions that estimate the lowest concentration of an antibiotic that will provide resistant bacteria an advantage over susceptible bacteria. Based on these insights, we sought to determine whether human exposure to selected antibiotics through ingestion of foodstuffs could result in colon concentrations exceeding apparent MSCs. Nine antibiotics-tetracycline, oxytetracycline, ciprofloxacin, sarafloxacin, erythromycin, spiramycin, tilmicosin, tylosin, and lincomycin-were selected for analysis. Dietary exposure was estimated either using published measured antibiotic concentrations in foodstuffs or using ADI values or food MRLs and a conservative diet. Using the ADI, the estimated antibiotic residue concentrations in the human colon of all antibiotics assessed may be up to a 1,000-fold greater than the predicted MSCs. When the dietary exposure assessment used MRLs or measured concentration in foodstuffs, the estimated concentrations were considerably lower but still within the MSC range for most of the foodstuffs assessed. These results suggest that the ingestion of antibiotic residues through food consumption may expose intestinal microbiota to antibiotic concentrations exceeding the MSC boundaries, thus favoring the growth of potential resistant bacteria. We suggest that MRL and ADI values be revisited in light of the recognition that antibiotic concentrations significantly below the MIC may select for resistance.