Animal organoids drive advances in One Health research

The use of animal organoids as three-dimensional models is driving advances in One Health research, enabling more realistic simulations of the interface between humans, animals, and the environment. These models accelerate the understanding of emerging infectious diseases and facilitate the development of prevention and control strategies.

Emerging infectious diseases, driven by factors such as climate change, urbanization, and the global trade in wild animals, pose increasing threats to public health, ecosystems, and biodiversity. The One Health concept, which recognizes the interconnectedness of human, animal, and environmental health, has become fundamental to addressing these challenges. However, the lack of experimental models that faithfully reproduce the complexity of these interactions has limited scientific progress. In this context, animal organoids have emerged as innovative tools capable of filling critical gaps in translational research.

According to García-Rodríguez and colleagues, organoids are three-dimensional structures cultured in vitro that reproduce the cellular composition, organization, and functions of the organ of origin. These models have already been established from tissues of various species, including cattle, birds, and bats, and are being applied in studies of cross-species infections, environmental toxicity, antimicrobial resistance, and pandemic preparedness. In cattle, Fritsch and collaborators developed mammary gland organoids capable of simulating infection by different subtypes of influenza A virus. The study showed that both avian-origin viruses (such as highly pathogenic H5N1) and strains of swine and human origin efficiently infected the organoids, while the avian H9N2 subtype showed restricted replication. This platform allows detailed investigation of mammary infection pathogenesis and zoonotic transmission risks, as well as supporting strategies for animal and public health protection.

In birds, Xiang and colleagues established goose kidney organoids to study astrovirus-induced gout, a fatal disease in goslings characterized by kidney injury and high mortality. The organoids maintained the physiological functions of the kidney and, when infected with the virus, reproduced the increase in uric acid observed in vivo. Infection modulated gene expression and cellular metabolism, mainly in purine pathways, providing a relevant model to elucidate disease mechanisms and test interventions.

In the context of the microbiota and intestinal health, Du and collaborators used ruminant colonic organoids to investigate the role of Faecalibacterium duncaniae in dairy calves with diarrhea. Treatment with metabolites derived from this bacterium reduced inflammatory responses, restored epithelial proliferation, and preserved the integrity of cell junctions, even under inflammatory stress induced by TNF-α. Transcriptomic analysis revealed suppression of inflammatory pathways and activation of repair mechanisms, indicating potential for microbiota-based nutritional strategies to reduce antimicrobial use and improve productivity.

Regarding wildlife reservoirs, Madden and colleagues highlighted the development of organoids from gastrointestinal, respiratory, and renal tissues of different bat species. These models showed increased expression of interferon genes and other antiviral mechanisms, both under basal conditions and in response to viral infection. The ability of organoids to sustain viral replication varied according to the virus, tissue, and bat species, reflecting the biological diversity of these animals. The results reinforce the potential of organoids to unravel specific immune responses and understand why bats are reservoirs of emerging viruses without developing clinical disease.

Despite advances, organoids have limitations. According to García-Rodríguez and colleagues, most models still lack immune system components, vascularization, and interaction with complex microbiota, all essential factors to fully simulate in vivo physiology. In addition, the response to infection may vary depending on cell origin, culture protocol, and infectious agent. Madden and collaborators emphasize that diversity among bat species and tissues results in different patterns of viral replication, requiring caution when extrapolating data. In birds, Xiang and colleagues observed that other avian viruses did not induce the same pattern of renal dysfunction in organoids, highlighting the model's specificity for goose astrovirus.

Animal organoids are bringing basic research closer to applied needs in One Health. They allow hypotheses about interspecies transmission to be tested, environmental toxicity to be assessed, antimicrobial resistance to be investigated, and nutritional or pharmacological interventions to be developed more quickly and ethically, reducing the use of live animals. The ability to model diseases specific to each species and environmental context expands the potential for more precise responses to outbreaks and emerging threats. As García-Rodríguez and colleagues noted, "organoids represent a bridge between fundamental science and translational solutions for global challenges".

In summary, the advancement of animal organoids as experimental models is redefining the study of emerging infectious diseases and other challenges at the human-animal-environment interface. Despite current limitations, these systems offer unprecedented opportunities to accelerate discoveries, integrate knowledge, and strengthen prevention and control strategies in One Health.