Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.

Abstract

Using a dextran sulfate sodium (DSS)-induced murine colitis model, this study examined how H₂ gas inhalation affects gut microbial composition and downstream inflammatory pathways. H₂ inhalation corrected DSS-induced dysbiosis by reducing potentially pathogenic taxa such as Enterobacteriaceae and Escherichia-Shigella while enriching beneficial genera including Bacteroides and Lactobacillaceae. Intestinal barrier integrity was restored through increased goblet cell density and upregulation of tight junction proteins ZO-1 and occludin. Immune balance was improved via normalization of the Treg/Th17 cell ratio. At the molecular level, suppression of TLR4/NF-κB signaling and activation of the Keap1/Nrf2 antioxidant axis were observed, accompanied by decreased pro-inflammatory cytokines, reduced oxidative stress markers, and elevated antioxidant enzyme activity. Fecal microbiota transplantation experiments corroborated these findings, supporting gut microbiome remodeling as a central mechanism underlying H₂-associated colitis alleviation.

Mechanism

H₂ inhalation reshapes gut microbial ecology, suppresses TLR4/NF-κB inflammatory signaling, and activates the Keap1/Nrf2 antioxidant pathway, collectively reducing cytokine production, oxidative stress, and intestinal barrier disruption in DSS-induced colitis.