Junli Xue

Molecular hydrogen (H ₂ ) 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 H ₂ . The GM serves as both a key site for endogenous H ₂ production and consumption, and a potential site of interaction with exogenous H ₂ supplementation, with possible implications for intestinal microecological homeostasis. This narrative review critically summarizes current evidence on the bidirectional relationship between H ₂ and the GM, focusing on microbial H ₂ production and consumption, the potential role of H ₂ in maintaining gut microbial homeostasis, and the impact of exogenous H ₂ supplementation on intestinal microecology. The potential therapeutic relevance of H ₂ -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 H ₂ may influence the GM ecosystem. However, most supporting data remains preclinical, and whether GM alterations causally mediate the biological or therapeutic effects of H ₂ remains to be established. Elucidating the reciprocal interaction between H ₂ and the GM may provide new mechanistic insight into H ₂ -based interventions and facilitate the development of microbiota-targeted therapeutic strategies for human diseases.