Antimicrobial drug residues in animal‐derived foods: Potential impact on the human intestinal microbiome

Abstract

The use of veterinary drugs in food‐producing animals may result in the presence of low levels of drug residues in these edible, animal‐derived foods, with potential dietary exposure to humans. Since therapeutic doses of antibiotics have been shown to affect bacterial populations in the gastrointestinal tract microbiome and can also promote the emergence of antibiotic‐resistant bacteria, there is concern that animal drugs at residue level concentrations could also perturb the intestinal microbiome composition and modify the antimicrobial resistance profile of the human intestinal microbiota. This review provides updated information on the VICH GL#36(R2), on evaluating the safety of veterinary drug residues in animal‐derived foods and their effects on the human intestinal microbiome; discusses critical research knowledge gaps and challenges in evaluating the impact of drug residues in animal‐derived foods on the human intestinal microbiome; and analyzes integrated basic and applied research approaches, currently being conducted at FDA, on studies that specifically address key regulatory science questions. Moreover, this review aims to emphasize future research needs on scientific methodology and provides general recommendations on drug inactivation, bioavailability, and antimicrobial resistance, to improve the safety evaluation and risk assessment of antimicrobial residues and their impact on the gastrointestinal microbiota, with the goal of ensuring food safety.

Impact of Chronic Tetracycline Exposure on Human Intestinal Microbiota in a Continuous Flow Bioreactor Model

“…Tetracycline and other antimicrobial drug residues may be present in edible tissues and meat products from treated food-producing animals. These residues are considered to be potential hazards because they can affect human intestinal microbiota composition, antimicrobial resistance, and intestinal permeability, leading to barrier disruption effects and selection of resistant intestinal bacteria [ 7 , 8 , 9 , 13 , 15 , 19 , 20 , 24 ]. Microbiological endpoints that should be considered when establishing a microbiological acceptable daily intake (mADI) are the disruption of the colonization barrier and the increase of resistant bacterial populations [ 9 ].…”

“…Microbiological endpoints that should be considered when establishing a microbiological acceptable daily intake (mADI) are the disruption of the colonization barrier and the increase of resistant bacterial populations [ 9 ]. Previously, researchers monitored intestinal bacteria composition changes within the predominant microbiota, changes in levels of volatile SCFAs, bacterial hydrolytic and reductive enzymes, emergence of resistance, barrier disruption endpoints, and drug bioavailability in the gastrointestinal tract to establish acceptable antimicrobial residue levels in food [ 7 , 14 , 15 , 16 , 17 , 18 , 19 , 25 , 26 , 27 ]. The goal of this study was to evaluate current approaches to measuring chronic exposure of tetracycline on human intestinal microbiota using a continuous flow bioreactor.…”

“…This allows overgrowth of pathogenic, opportunistic, or resistant microorganisms, potentially altering the ecological balance of the microbial community [ 4 , 5 , 6 ]. Despite the enormous amount of data on the effects of antimicrobials used in human medicine at therapeutic dose levels, which cause increased incidence of antimicrobial resistance, little is known regarding chronic or long-term exposure of residual veterinary drug levels in food, which could affect bacteria in the gastrointestinal tract and induce resistance [ 7 , 8 , 9 ]. The acceptable daily intake (ADI) is based on an array of toxicological, microbiological, and pharmacological data used in safety evaluations that take into account acute, chronic, and long-term exposure by ingestion of veterinary drug residues in food [ 7 ].…”

“…Despite the enormous amount of data on the effects of antimicrobials used in human medicine at therapeutic dose levels, which cause increased incidence of antimicrobial resistance, little is known regarding chronic or long-term exposure of residual veterinary drug levels in food, which could affect bacteria in the gastrointestinal tract and induce resistance [ 7 , 8 , 9 ]. The acceptable daily intake (ADI) is based on an array of toxicological, microbiological, and pharmacological data used in safety evaluations that take into account acute, chronic, and long-term exposure by ingestion of veterinary drug residues in food [ 7 ]. There are potential hazards of antimicrobial drug residues in food that include adverse effects on human intestinal microbiota composition, antimicrobial resistance, and intestinal permeability, leading to barrier disruption effects and selection of resistant intestinal bacteria [ 7 , 8 , 9 ].…”

“…The acceptable daily intake (ADI) is based on an array of toxicological, microbiological, and pharmacological data used in safety evaluations that take into account acute, chronic, and long-term exposure by ingestion of veterinary drug residues in food [ 7 ]. There are potential hazards of antimicrobial drug residues in food that include adverse effects on human intestinal microbiota composition, antimicrobial resistance, and intestinal permeability, leading to barrier disruption effects and selection of resistant intestinal bacteria [ 7 , 8 , 9 ].…”