Modeling and Analysis of SCFA-Driven Vagus Nerve Signaling in the Gut-Brain Axis via Molecular Communication

Abstract: Molecular communication (MC) is a bio-inspired communication paradigm that utilizes molecules to transfer information and offers a robust framework for understanding biological signaling systems. This paper introduces a novel end-to-end MC framework for short-chain fatty acid (SCFA)-driven vagus nerve signaling within the gut-brain axis (GBA) to enhance our understanding of gut-brain communication mechanisms. SCFA molecules, produced by gut microbiota, serve as important biomarkers in physiological and psychological processes, including neurodegenerative and mental health disorders. The developed end-to-end model integrates SCFA binding to vagal afferent fibers, G protein-coupled receptor (GPCR)-mediated calcium signaling, and Hodgkin-Huxley-based action potential generation into a comprehensive vagus nerve signaling mechanism through GBA. Information-theoretic metrics such as mutual information and delay are used to evaluate the efficiency of this SCFA-driven signaling pathway model. Simulations demonstrate how molecular inputs translate into neural outputs, highlighting critical aspects that govern gut-brain communication. In this work, the integration of SCFA-driven signaling into the MC framework provides a novel perspective on gut-brain communication and paves the way for the development of innovative therapeutic advancements targeting neurological and psychiatric disorders.