Cities as Biological Systems: An Ontology of Urban Exposure, Health, and Evolutionary Change

Urbanization concentrates chemical, physical, social, and microbial exposures in the same spatial environment, and a growing body of genomic, epigenomic, and evolutionary evidence shows that this exposure environment leaves measurable biological traces. This review proposes a single causal architecture, the Urban Exposome framework, that traces urban exposure from the environment through a defined sequence of biological layers (exposure, biological interface, molecular response, biological state, phenotype, health outcome) to, in a separate and explicitly non-equivalent branch, population-level evolutionary change. Using this architecture, we synthesize evidence that urban exposures induce oxidative stress, DNA damage, epigenomic remodeling, and non-coding RNA responses in humans; reshape the human and environmental microbiome and the ecology of antimicrobial resistance; and act as a selective force on wildlife and microbial populations. We show that these responses operate on fundamentally different timescales and inheritance regimes: humans predominantly exhibit life-course physiological plasticity and developmental programming; microbial communities change within days through ecological turnover and horizontal gene transfer; and some wildlife populations show heritable, population-genetic adaptation. Health outcomes are organized into five mechanistically grounded disease clusters rather than repeated across chapters. We argue that the value of an Urban Exposome framework is not to collapse these phenomena into a single form of "evolution," but to connect them within one causal architecture while preserving their biological and evidentiary distinctions, a foundation for precision urban health, One Health surveillance, and evidence-based urban design.