The Exposome Surveillance Hypothesis an Integrative Systems Biology Framework for Environmental Information Processing, Adaptive Regulation, and Chronic Disease

Kurt E Müller, Martina Wagner.

Abstract

The Exposome Surveillance Hypothesis proposes that health depends on the continuous detection, interpretation, and biological processing of environmental information. Environmental exposures are conceptualised not only as potential sources of injury but also as signals that must be integrated by distributed molecular sensors, barrier tissues, neuroimmune pathways, endocrine networks, autonomic regulation, and mitochondrial signalling. We introduce the Environmental Surveillance System (ESS) as a functional systems biology framework for this distributed information processing architecture and position the Neuroendocrine-Immune System as its principal adaptive effector network. Transient receptor potential vanilloid 1 is presented as a prototype sentinel receptor illustrating how heterogeneous physical, chemical, inflammatory, and metabolic signals can be translated into calcium-dependent neuroimmune and mitochondrial responses. Within this framework, Adaptive Capacity denotes the organism’s integrated ability to respond and recover, whereas Adaptive Debt describes the cumulative unresolved biological burden that develops when recovery remains incomplete. Progressive Adaptive Debt may reduce regulatory flexibility, promote self-perpetuating maladaptation, and contribute to convergent patterns of chronic inflammation, autonomic dysfunction, mitochondrial impairment, pain, fatigue, and multisystem disease. Finally, Guided Restoration of Adaptive Biological Self-Regulation is introduced as a translational framework aimed at identifying and reducing biological constraints before gradually restoring adaptive capacity. The hypothesis generates testable predictions concerning preclinical network dysfunction, multidimensional biomarkers, disease convergence, and reversibility of maladaptive regulation.