Antibiotic resistance in humans and farm animals poses a major health challenge. A new study published in the journal ‘Nature Communications’ reveals that this problem does not stop at hospital doors or farm gates – indeed, antibiotic resistance genes (ARGs) can also be detected in wild animals. A team led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW) and the Max Delbrück Center has shown that wild mice on farms carry around 50 percent of the ARGs found in cattle, pigs or poultry, and that the intensity of livestock farming, amongst other factors, plays a decisive role in determining which and how many resistance genes are transferred into the mice’s microbiome.

For the study, the scientists analysed the genomes of gut microorganisms from an extensive population of 875 wild house mice (Mus musculus) collected from farms in Germany. They searched for genes responsible for resistance to common antibiotics and correlated the presence of these ARGs in the mice with a range of environmental and host variables, such as land use and farming practices, livestock density for cattle, pigs and poultry, sex and physical condition of the mice, as well as climatic variables. These statistical analyses aim to explain the influence these factors have on which and how many ARGs are present in the mice’s gut microbiome. In a second step, they compared the resistance profiles in the mice’s genomes with resistance genes found in the manure of farm animals, whose genomic data is publicly available from other projects.

Half of the resistance genes found in farm animals are also found in mice
Previous studies have shown that water bodies in urban areas and agricultural land are heavily contaminated with antibiotic-resistant bacteria. The scientists therefore expected that antibiotic resistance would also be detected in wild animals in the immediate vicinity of large livestock farms. “We had no idea of the extent to which the transference of resistance genes might be detected in wild animals,” says Dr Víctor Hugo Jarquín-Díaz of the Max Delbrück Center. “We expected some overlap, but we were surprised to find that around 50 percent of the resistance genes from cattle, pigs and chicken were also present in our wild mice.” This shows that there are many ecological bridges between humans, farm animals and wildlife, and that spatial proximity can always imply functional, ecological interdependence – and, in the case of antibiotic-resistant bacteria, indeed does.

Furthermore, the scientists found that environmental variables and the intensity of livestock farming have a greater influence on the specific resistance profile in the gut microbiome of a wild farm mouse than the mouse’s own characteristics. The way in which agricultural land in the immediate vicinity of the farm is used, and the resulting direct and indirect contact with farm animals, explains three times as well which ARGs are detectable in the mouse as the mouse’s sex or its body condition. “Our statistical models showed that certain factors have a very strong effect on the presence of specific resistance genes,” says Prof Emanuel Heitlinger, who conducted this study in the Humboldt-Universität zu Berlin and the Leibniz-IZW and is now associated with the Federal State Agency for Consumer & Health Protection Rhineland-Palatinate. “For example, pig farming density is strongly associated with resistance genes related to antibiotics that are widely and commonly used in veterinary and farming practices such as sulfonamide, tetracycline or beta-lactams.” There are therefore direct, demonstrable effects of intensive livestock farming on specific forms of antibiotic resistance in wildlife.

Antibiotic resistance must be analysed, understood and tackled in a more holistic manner
According to the team of authors, ecological concepts have so far been only insufficiently integrated into microbiome research. The study highlights that there are highly relevant links between hosts, microbiomes, resistance genes and spatial environmental factors. “We were able to identify pathways of resistance extending beyond the boundaries of medical or agricultural systems into the environment”, says Prof Stephanie Kramer-Schadt, Head of Department at the Leibniz-IZW and Professor at Technische Universität Berlin. “Antibiotic resistance is not an isolated medical problem, but a systemic ecological phenomenon. Our research represents the first step towards creating a clear ‘map’ of how ecosystems heavily used and shaped by humans influence the evolution of microorganisms in the environment.” The team argues that resistance monitoring must therefore be expanded and move away from its focus on clinical or livestock contexts. Wild animals and natural ecosystems could be a major unknown in this equation and represent unexpected reservoirs of antibiotic resistance.