An Explainable Knowledge Graph-Driven Approach to Decipher the Link Between Brain Disorders and the Gut Microbiome

The communication between the gut microbiome and the brain, known as the microbiome-gut-brain axis (MGBA), is emerging as a critical factor in neurological and psychiatric disorders. This communication involves complex pathways including neural, hormonal, and immune interactions that enable gut microbes to modulate brain function and behavior. However, the specific mechanisms through which gut microbes influence brain function remain poorly understood, and existing computational efforts to understand these mechanisms are simplistic or have limited scope. This work presents a comprehensive approach for understanding these mechanisms by elucidating the cascade of interactions that allows gut microbes to influence brain disorders. By using a large curated biomedical knowledge graph, we train GNN-GBA, an explainable graph neural network, to learn the complex biological interactions between the gut microbiome and the brain. GNN-GBA is then used to extract the mechanistic pathways through which the gut microbiome can influence brain disorders. The network successfully identified pathways for 103 brain disorders, and we show that these pathways are consistent with existing literature. An interactive dashboard to explore thousands of potential mechanisms through which the gut microbiome can influence brain diseases is available at https://sds-genetic-interaction-analysis.opendfki.de/gutbrain/. [email protected]