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. © 2015 IEEE.