QSP Modeling Reveals How Citicoline Impacts Brain Health, Researchers Find

Kirin Holdings Company, Limited and Fujitsu Limited have jointly elucidated a novel gut-brain axis mechanism associated with citicoline through the first worldwide application of Quantitative Systems Pharmacology (QSP) models.

This research, conducted in December 2025, combined Fujitsu’s advanced QSP technologies with cell-based experimental validation to analyze citicoline, a compound manufactured by Kyowa Hakko Bio and widely used to support cognitive health. The study represents a pioneering example of utilizing AI-driven digital transformation (DX) technologies in food functionality research, offering a new approach to demonstrating efficacy without reliance on animal testing and potentially accelerating innovative health solutions. AI and DX Technology in Health Science Research Kirin and Fujitsu jointly conducted research applying AI-driven digital transformation (DX) technologies to health science, specifically investigating citicoline’s functionality. They utilized Quantitative Systems Pharmacology (QSP) models—an information science approach integrating physiological networks—combined with cell-based experiments.

This research identified a previously unknown mechanism within the gut-brain axis related to citicoline, a compound already used to support cognitive health, demonstrating a novel application of AI in food functionality research. The study employed AI-based analysis to predict that citicoline activates neuronal signaling through the gut. This prediction was then validated in vitro, confirming citicoline’s effect on intestinal pathways using a co-culture system of cells and neurons. Simulations using QSP models indicated citicoline enhances cholinergic signaling and increases acetylcholine levels in intestinal synapses, providing specific details about the mechanism by which citicoline may impact brain function via the gut.

This research represents a pioneering example of full-scale DX technology application in food functionality. The combined approach of AI-based prediction and experimental validation aims to improve the reliability of demonstrating efficacy without animal testing. Kirin and Fujitsu anticipate these findings will accelerate the adoption of AI-driven DX technologies within health science, potentially leading to innovative food solutions for longevity and well-being. Citicoline’s Role in the Gut-Brain Axis This research identified a previously unknown mechanism within the gut-brain axis associated with citicoline, utilizing QSP models and experimental validation. The study combined AI-based predictions with cell-based experiments, revealing that oral citicoline enhances cholinergic signaling in the gut-nerve axis. Simulations demonstrated a dose-dependent increase in acetylcholine levels within intestinal synapses, suggesting a direct impact on neuronal communication via the gut. Further validation confirmed citicoline’s ability to activate neuronal signaling through the intestinal pathway using an in vitro co-culture system of intestinal epithelial cells and neurons. This finding is significant because gut nerves are closely interconnected with the brain, elucidating part of citicoline’s gut-brain mechanism. Researchers utilized Kirin’s proprietary data and literature reviews to construct the QSP model evaluating citicoline’s functional properties. The research represents a pioneering example of applying DX technologies to food functionality research. The findings provide insights into citicoline’s physiological functions, potentially enhancing its value as a functional ingredient supporting brain health. Citicoline is an endogenous compound and a precursor to phosphatidylcholine, contributing to neuroprotection by supporting brain cell membrane repair and maintenance. Conventional drug discovery is time-consuming and costly, with limitations in improving confidence in demonstrating efficacy in humans. QSP Modeling and In Silico Simulation Kirin and Fujitsu utilized Quantitative Systems Pharmacology (QSP) models – an information science integrating physiological networks into computational models – in their research on citicoline. These QSP models, developed with Nova In Silico SAS, were combined with cell-based experimental validation to identify a previously unknown gut-brain axis mechanism associated with citicoline. This approach represents a full-scale application of AI-driven digital transformation (DX) technologies to food functionality research, aiming to improve efficacy demonstration without animal testing. Simulations using the QSP model predicted that oral citicoline administration enhances cholinergic signaling in the gut-nerve axis, inducing a dose-dependent increase in acetylcholine levels within intestinal synapses. These predictions were supported by in vitro experimental validation, confirming citicoline’s activation of neuronal signaling through an intestinal pathway using a co-culture system of epithelial cells and neurons.

This research elucidates part of the gut-brain mechanism of citicoline, enhancing its value as a functional ingredient. This study represents a pioneering example of applying DX technologies in the Health Science domain. The combination of QSP modeling and experimental validation allowed researchers to predict and confirm citicoline’s impact on the gut-brain axis, potentially leading to innovative food solutions supporting brain function and overall well-being. This methodology aims to accelerate R&D while addressing constraints on animal testing and diversifying medical needs.

This research represents a globally pioneering example of the full-scale application of DX technology in food functionality research. Citicoline’s Mechanism and Neuronal Signaling This research utilized Quantitative Systems Pharmacology (QSP) models and AI to investigate citicoline’s functionality, identifying a previously unknown mechanism within the gut-brain axis. Simulations predicted that oral citicoline enhances cholinergic signaling in the gut-nerve axis and increases acetylcholine levels within intestinal synapses. These predictions were validated through in vitro experimental work, confirming citicoline’s activation of neuronal signaling via an intestinal pathway using a co-culture system of intestinal epithelial cells and neurons. The study demonstrated that citicoline can activate neuronal signaling through the gut, validated by in vitro experimentation. Researchers constructed a QSP model utilizing Kirin’s proprietary data and literature to evaluate citicoline’s functional properties. This approach allowed for simulation-based evaluation of ligand-binding cholinergic receptors in enteric neurons and acetylcholine levels within intestinal synapses, providing a detailed look at the mechanism. Citicoline is an endogenous compound and a precursor to phosphatidylcholine, a key component of neuronal membranes. This contributes to neuroprotection through the support of brain cell membrane repair and maintenance. The research highlights citicoline’s potential value as a functional ingredient for health, by elucidating new physiological functions and contributing to a better understanding of the gut-brain connection. Kirin and Fujitsu’s Collaborative Research Kirin and Fujitsu collaborated on research utilizing Quantitative Systems Pharmacology (QSP) models – an AI-driven digital transformation (DX) technology – to investigate citicoline’s functionality.

This research aimed to identify novel mechanisms within the gut-brain axis, specifically concerning citicoline, a compound known for supporting cognitive health. The study combined virtual subject simulations—developed by Fujitsu and Nova In Silico SAS—with cell-based experimental validation to demonstrate efficacy without relying on traditional animal testing. The collaborative research predicted, through AI-based analysis, that oral citicoline administration enhances cholinergic signaling in the gut-nerve axis and increases acetylcholine levels within intestinal synapses. These predictions were then confirmed in vitro using a co-culture system of intestinal epithelial cells and neurons, demonstrating citicoline’s ability to activate neuronal signaling through the intestinal pathway. This validated the hypothesis that citicoline impacts the gut-brain connection. This study represents a pioneering application of DX technologies in food functionality research, offering insights into citicoline’s physiological functions and its potential as a functional ingredient for health. Kirin and Fujitsu’s work aims to contribute to realizing a society that promotes longevity and well-being through innovative food solutions, and the companies intend for the research to be used for B2B purposes in overseas markets. Source: https://www.kirinholdings.com/en/newsroom/release/2025/1217_01.html Tags: