Systems Level Model of Dietary Effects on Cognition via the Microbiome-Gut-Brain Axis

Intercommunication of the microbiome-gut-brain axis occurs through various signaling pathways including the vagus nerve, immune system, endocrine/paracrine, and bacteria-derived metabolites. But how these pathways integrate to influence cognition remains undefined. In this paper, we create a systems level mathematical framework comprised of interconnected organ-level dynamical subsystems to increase conceptual understanding of how these subsystems contribute to cognitive performance. With this framework we propose that control of hippocampal long-term potentiation (hypothesized to correlate with cognitive performance) is influenced by interorgan signaling with diet as the external control input. Specifically, diet can influence synaptic strength (LTP) homeostatic conditions necessary for learning. The proposed model provides new qualitative information about the functional relationship between diet and output cognitive performance. The results can give insight for optimization of cognitive performance via diet in experimental animal models.