Gut-Brain Axis as a Closed-Loop Molecular Communication Network

Abstract: Molecular communication (MC) provides a quantitative framework for analyzing information transfer within biological systems. This paper introduces a novel and comprehensive MC framework for the gut-brain axis (GBA) as a system of six coupled, nonlinear delay differential equations (DDEs). The proposed model defines a bidirectional feedback loop with a gut-to-brain inflammatory channel and a brain-to-gut neuroendocrine channel. Under prolonged stress, this feedback loop becomes self-perpetuating and drives the system into a pathological state. We evaluate the end-to-end channel across varying conditions using time-domain simulations, small-signal frequency-domain characterization, and an information-theoretic capacity analysis. At homeostasis, the system maintains stable circadian dynamics with higher information throughput, whereas sustained stress drives a shift to dysregulated hypercortisolism. In this pathological state, spectral efficiency decreases due to a narrowed effective bandwidth and a lower passband gain driven by neuroendocrine delays and saturating cytokine-hormone kinetics. These results quantify the impact of these signaling mechanisms on stability and information processing, elucidating the transition from healthy circadian rhythms to a persistent pathological state of hypercortisolism.