# Gut microbiota as a central mediator in hydrogen gas-induced alleviation of colitis via TLR4/NF-κB and Nrf2 pathway regulation.
> 腸内細菌叢を介した水素ガス吸入による大腸炎軽減：TLR4/NF-κBおよびNrf2経路の関与


## 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.

## Bibliographic

- **Authors**: Shi W, Xi M, Zhang K, Yang J, Cheng X, Zang H, et al.
- **Journal**: Int Immunopharmacol
- **Year**: 2025 (2025-12-10)
- **PMID**: [41076929](https://pubmed.ncbi.nlm.nih.gov/41076929/)
- **DOI**: [10.1016/j.intimp.2025.115671](https://doi.org/10.1016/j.intimp.2025.115671)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41076929. https://h2-papers.org/en/papers/41076929
> **Source**: PubMed PMID [41076929](https://pubmed.ncbi.nlm.nih.gov/41076929/)