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Gut health affects mental health through gut-to-brain signaling, but how these gut signals cross the blood-brain barrier (BBB) to communicate with neurons in the brain remains unclear. We propose that gut signals target glial cells in the BBB, which relay messages to neurons in the brain. Using advanced bioimaging and genetics, we aim to uncover this novel gut-brain communication pathway via glial cells in the BBB. If confirmed, our findings could transform the understanding of the gut-brain axis, identify glial cells as accessible drug targets, and potentially pave the way for innovative treatments for conditions such as depression and anxiety.