Molecular hydrogen may influence gut microbiota and intestinal barrier integrity in metabolic and gastrointestinal disordersMolecular Hydrogen May Influence Gut Health and Metabolic Diseases

Molecular hydrogen (H2) has emerged as a promising bioactive gas with well-documented antioxidant, anti-inflammatory, and cytoprotective properties, and its therapeutic potential for a range of human diseases has been increasingly recognized. Accumulating evidence suggests that the gut microbiota (GM) may contribute to some of the biological effects of H2. The GM serves as both a key site for endogenous H2 production and consumption, and a potential site of interaction with exogenous H2 supplementation, with possible implications for intestinal microecological homeostasis. This narrative review critically summarizes current evidence on the bidirectional relationship between H2 and the GM, focusing on microbial H2 production and consumption, the potential role of H2 in maintaining gut microbial homeostasis, and the impact of exogenous H2 supplementation on intestinal microecology. The potential therapeutic relevance of H2-associated GM modulation is further discussed in metabolic diseases, gastrointestinal disorders, and neurodegenerative diseases. Proposed mechanisms include regulation of microbial composition, reinforcement of intestinal barrier integrity, suppression of inflammation and oxidative stress, modulation of microbial metabolites, and gut-organ axis signaling. Collectively, current evidence supports that H2 may influence the GM ecosystem. However, most supporting data remains preclinical, and whether GM alterations causally mediate the biological or therapeutic effects of H2 remains to be established. Elucidating the reciprocal interaction between H2 and the GM may provide new mechanistic insight into H2-based interventions and facilitate the development of microbiota-targeted therapeutic strategies for human diseases.