Organ-on-Chip Models of Microbiota-Associated Cardiovascular and Neurovascular Signaling: Molecular Transport, Tissue Exposure, and Functional Responses

Gut microbiota-associated molecules influence cardiovascular and neurovascular physiology through microbial production, intestinal transfer, host transformation, and systemic delivery. Organ-on-chip (OoC) and microphysiological systems (MPSa) provide experimental platforms for investigating these processes across human tissue interfaces. However, nominal molecular input does not necessarily represent exposure at the responding tissue. This difference complicates comparisons across experimental platforms. This review examines intestinal, inter-organ, cardiovascular, and neurovascular MPS along the pathway from microbial signal generation to tissue response. It examines how material interactions, fluidic conditions, and biological transport processes determine molecular delivery. Evidence across platforms shows that compound recovery and downstream concentration vary with molecular properties and device materials. Cardiovascular and neurovascular studies further relate defined molecular exposure conditions to endothelial, thrombotic, cardiac, and neurovascular responses. Comparisons of compound recovery, compartmental concentrations, mass balance, and functional responses clarify the factors influencing molecular delivery and biological effects across OoC/MPS platforms. This review highlights the importance of quantifying molecular delivery and tissue exposure when interpreting functional responses across OoC/MPS platforms.