Individual variability in hydrogen-producing microbes influences the response to hydrogen supplementation on sleep quality: a randomized, double-blind, placebo-controlled, parallel study

Abstract Hydrogen has been reported to exert antioxidant and anti-inflammatory effects, and its potential health benefits have been investigated. However, to our knowledge, evidence regarding its impact on sleep quality in healthy individuals remains extremely limited. In addition, the influence of inter-individual variability in the gut microbiota on hydrogen efficacy has seldom been studied. In this study, we aimed to assess the impact of hydrogen-rich jelly on sleep quality and examine the influence of gut microbiota on this effect. A total of 44 healthy adults with poor sleep quality were randomized to receive either hydrogen-rich jelly or placebo jelly. No significant differences were observed between the intervention groups in the changes in sleep-related outcomes, including OSA-MA, VAS, PSQI, and STAI scores, in the overall analysis. Notably, when participants were stratified by the mean change in the VAS score for sleep quality, gut microbiota β-diversity showed apparent clustering in the hydrogen group but not in the placebo group. This cluster was explained by the differences in the relative abundance of hydrogen-producing bacteria, such as Bacteroides . Linear mixed-effects model analyses revealed significant interaction effects in the group × H 2 -producers in the VAS for sleep quality and mental stress, with greater improvement in participants with a lower abundance of hydrogen-producing bacteria. In conclusion, these exploratory findings raise the hypothesis that baseline gut microbiota composition, particularly microbial hydrogen-producing capacity, may modify individual responses to hydrogen supplementation. This hypothesis warrants confirmation in larger studies to explore its implications for microbiome-informed stratification in future hydrogen intervention research. Clinical trial registration : This clinical trial was registered with the University Hospital Medical Information Network Clinical Trial Registry on 27/12/2023 (UMIN-CTR, UMIN000053237).