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

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Hauptverfasser: Ortlek, Beyza E., Akan, Ozgur B.
Format: Preprint
Veröffentlicht: 2025
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author Ortlek, Beyza E.
Akan, Ozgur B.
author_facet Ortlek, Beyza E.
Akan, Ozgur B.
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2509_07911
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Gut-Brain Axis as a Closed-Loop Molecular Communication Network
Ortlek, Beyza E.
Akan, Ozgur B.
Emerging Technologies
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.
title Gut-Brain Axis as a Closed-Loop Molecular Communication Network
topic Emerging Technologies
url https://arxiv.org/abs/2509.07911