Abstract
Molecular hydrogen (H(2)), recognized as the smallest gas molecule, is capable of permeating cellular membranes and diffusing throughout the body. Due to its high bioavailability, H(2) is considered a therapeutic gas for the treatment of various diseases. The therapeutic efficacy of hydrogen is contingent upon factors such as the administration method, duration of contact with diseased tissue, and concentration at targeted sites. H(2) can be administered exogenously and is also produced endogenously within the intestinal tract. A comprehensive understanding of its delivery mechanisms and modes of action is crucial for advancing hydrogen medicine. This review highlights H₂'s mechanisms of action, summarizes its administration methods, and explores advancements in treating intestinal diseases (e.g., inflammatory bowel disease, intestinal ischemia-reperfusion, colorectal cancer). Additionally, its applications in managing other diseases are discussed. Finally, the challenges associated with its clinical application and potential solutions are explored. We propose that current delivery challenges faced by H(2) can be effectively addressed through the use of nanoplatforms; furthermore, interactions between hydrogen and gut microbiota may provide insights into its mechanisms for treating intestinal diseases. Future research should explore the synergistic effects of H(2) in conjunction with conventional therapies and develop personalized treatment plans to achieve precision medicine.