Ingestion of Milk Containing Very Low Concentration of Antimicrobials: Longitudinal Effect on Fecal Microbiota Composition in Preweaned Calves

Abstract

Although antimicrobial drugs are central to combat disease in modern medicine, the use of these drugs can have undesired consequences for human and animal health. One consequence is the post-therapy excretion of pharmacological agents, such as the elimination of drug residues at very low concentrations in the milk of lactating mammals. Limited information is currently available on the impact from the exposure of the gut microbiota to drug residues using in vivo natural models. The objective of our study was to address this knowledge gap and evaluate the effect on the fecal microbiota composition from feeding preweaned dairy calves raw milk with residual concentrations of ampicillin, ceftiofur, penicillin, and oxytetracycline from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR), and 15 calves were fed raw milk with drug residues (DR) by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 μg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth, prior to the first feeding in the trial (pre-treatment), until 6 weeks of age. Sequencing of the microbial 16S rRNA genes was conducted using the Illumina MiSeq, which provides a high resolution of the microbiota down to the genus level. Discriminant analysis showed that, except for pre-treatment samples, calves fed milk with drug residues and calves fed milk without drug residues easily discriminated at the genus level on their weekly microbial profile. However, analysis comparing the abundance of taxon between NR and DR showed significant differences only at the genus levels, and not at the phylum, class, order or family levels. These results suggest that although drug residues can result in clear discriminate gut microbial communities, they do not result in disruption of taxonomic levels above the genus.

Antimicrobial usage and resistance in beef production

“…Pereira et al [163] characterized the gut microbiota (fecal samples) of pre-weaned dairy calves fed raw milk spiked with ‘residual’ concentrations of ceftiofur (ceftiofur sodium; 0.1 μg/mL), ampicillin (ampicillin sodium; 0.01 μg/mL), penicillin (penicillin G sodium; 0.005 μg/mL), and oxytetracycline (oxytetracycline hydrochloride; 0.3 μg/mL) using 16S rRNA Illumina MiSeq-based sequencing. Exposure resulted in Genus-level differences, but taxa above the Family level were not altered [163].…”

“…Exposure resulted in Genus-level differences, but taxa above the Family level were not altered [163]. The microbiota of exposed calves was also less diverse than treatment-free calves [163].…”

“…Exposure resulted in Genus-level differences, but taxa above the Family level were not altered [163]. The microbiota of exposed calves was also less diverse than treatment-free calves [163]. Similarly, Reti et al [162] examined the effects of a sub-therapeutic AGP on the abundance and composition of microflora in the small and large intestine of adult beef cattle.…”

Food Additives and Contaminants: Effects on Human Gut Microbiota—A Review

“…This can influence the health of the host, particularly if the bacterial group that is decimated, affects a physiological health-related function [3]. [120] Prospective trial in animal models (calves)…”

“…Only a few works have focused on the effects of low concentrations of antibiotics on the GM [109,110,120]. This is surprising because antibiotics are the most widely used drugs in the livestock industry in the world [127] and their residues can reach humans through animal feeds.…”