Impact of Antibiotic Therapies on Resistance Genes Dynamic and Composition of the Animal Gut Microbiota

SIMPLE SUMMARY: Antibiotics perturb the gastrointestinal microbiota by killing bacteria beneficial for animal health and favoring the emergence of potential pathogens. Furthermore, antibiotics favor the emergence of resistant bacteria. Current knowledge on animals’ intestinal microbiota and effects of antibiotics is blurred by the various posology, administration routes, and implemented methodologies for its analysis. We summarized 71 studies analyzing the administration of antibiotics by different routes, conducted on the main food-producing and companion animals, highlighting differences in the methodology applied for the intestinal microbiota and antibiotic resistance analysis. Overall, therapeutic dosage decreased bacterial species diversity and richness in the microbiota and selected antibiotic resistance genes. For non-therapeutic dosage, information on the selection of antibiotic resistance was scarce and the effect on the intestinal microbiota scattered. Understanding the gut microbiota composition and function in animals could open up strategies for its modulation to improve animal health and performance, and to minimize the negative impact of antibiotics. ABSTRACT: Antibiotics are major disruptors of the gastrointestinal microbiota, depleting bacterial species beneficial for the host health and favoring the emergence of potential pathogens. Furthermore, the intestine is a reactor of antibiotic resistance emergence, and the presence of antibiotics exacerbates the selection of resistant bacteria that can disseminate in the environment and propagate to further hosts. We reviewed studies analyzing the effect of antibiotics on the intestinal microbiota and antibiotic resistance conducted on animals, focusing on the main food-producing and companion animals. Irrespective of antibiotic classes and animal hosts, therapeutic dosage decreased species diversity and richness favoring the bloom of potential enteropathogens and the selection of antibiotic resistance. These negative effects of antibiotic therapies seem ineluctable but often were mitigated when an antibiotic was administered by parenteral route. Sub-therapeutic dosages caused the augmentation of taxa involved in sugar metabolism, suggesting a link with weight gain. This result should not be interpreted positively, considering that parallel information on antibiotic resistance selection was rarely reported and selection of antibiotic resistance is known to occur also at low antibiotic concentration. However, studies on the effect of antibiotics as growth promoters put the basis for understanding the gut microbiota composition and function in this situation. This knowledge could inspire alternative strategies to antibiotics, such as probiotics, for improving animal performance. This review encompasses the analysis of the main animal hosts and all antibiotic classes, and highlights the future challenges and gaps of knowledge that should be filled. Further studies are necessary for elucidating pharmacodynamics in animals in order to improve therapy duration, antibiotic dosages, and administration routes for mitigating negative effects of antibiotic therapies. Furthermore, this review highlights that studies on aminoglycosides are almost inexistent, and they should be increased, considering that aminoglycosides are the first most commonly used antibiotic family in companion animals. Harmonization of experimental procedures is necessary in this research field. In fact, current studies are based on different experimental set-up varying for antibiotic dosage, regimen, administration, and downstream microbiota analysis. In the future, shotgun metagenomics coupled with long-reads sequencing should become a standard experimental approach enabling to gather comprehensive knowledge on GIM in terms of composition and taxonomic functions, and of ARGs. Decorticating GIM in animals will unveil revolutionary strategies for medication and improvement of animals’ health status, with positive consequences on global health.