Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial

Abstract

Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events.

Study details

Article type

Original Research

Disease / injury model

Ulcerative colitis (human, active disease)

Duration

8 weeks

Dose comparison

All participants in the hydrogen group received the same concentration and dose of hydrogen gas (5–6% at 4 L/min for 4 hours daily).

Dose-dependent effect

No

Outcome

Neutral

Findings

Hydrogen gas inhalation increased intestinal microbiota diversity (notably β-diversity) in patients with ulcerative colitis, but did not produce a statistically significant improvement in clinical outcomes compared to placebo. No adverse events were observed.