Host-Microbe-Epigenome Interactions: Unlocking Novel Therapeutics for Zoonotic Disease Prevention

Document Type : Review Article

Authors

1 Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Selcuk University, Konya, Turkey

2 Department of Agriculture, Jo.C, Islamic Azad University, Jouybar, Iran

3 National Institute of Food Science and Technology, University of Agriculture, Faisalabad, 38000, Pakistan

4 Department of Biology, Faculty of Science, University of Zakho, Zakho, Duhok, Iraq

5 Department of Medical Biology, Medicine Faculty, Nigde Omer Halisdemir University, Nigde, Türkiye.

6 Western Caspian University, Baku, Azerbaijan.

7 Department of Biology, Faculty of Sciences, Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkestan, Kazakhstan

10.22092/ari.2025.369880.3709

Abstract

Zoonotic diseases remain pertinent and significant contributors to global morbidity and mortality, fuelled by expanding human-animal interface, ecological disruption, and microbial evolution. Even as traditional therapeutic approaches largely aim at pathogens themselves, insight into the host–microbe–epigenome triad holds revolutionary promise in managing zoonoses. This review integrates insights into how microbial communities and their metabolites—especially of gut, respiratory, and cutaneous microbiomes—regulate host immunity by epigenetic processes such as DNA methylation, histone modification, and non-coding RNA function. Microbial exposure—commensal or pathogen—can induce host epigenetic remodelling. Epigenetic mechanisms are central mediators of host-pathogen interaction, regulating gene expression patterns controlling innate and adaptive immunity. We discuss how these molecular events are affected by infection with major zoonotic pathogens like SARS-CoV-2, H5N1, Leptospira, and Leishmania to result in immune suppression, chronic inflammation, or disrupted host susceptibility. Notably, microbial-derived metabolites, such as short-chain fatty acids, have been demonstrated to reprogram host epigenomes by modulating histone deacetylases, thus offering potential therapeutic leverage points. Through rigorous literature mining and bioinformatic filtering, we identify epigenetically regulated host biomarkers as well as microbial signals relevant for diagnostic and therapeutic targeting. In addition, we assess the effectiveness of epigenetic therapeutics—such as HDAC and DNA methyltransferase inhibitors—to prevent the zoonotic infection pathogenesis in preclinical models. The review advocates for a harmonized therapeutic strategy that takes host epigenetic flexibility, microbial community, and immune memory into account. By focusing on this multifaceted interface, we hope to construct a conceptual model for the next generation of zoonotic disease treatments that are robust, targeted, and responsive to new-emerging pathogens.

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