# Molecular hydrogen suppresses gut inflammation and pyroptosis in ulcerative colitis through promoting PKM2 lactylation to block NLRP3 inflammasome activation.
> 分子状水素はPKM2ラクチル化を促進してNLRP3インフラマソーム活性化を抑制し、潰瘍性大腸炎における腸管炎症とパイロトーシスを軽減する


## Abstract

This study investigated the mechanisms by which molecular hydrogen affects ulcerative colitis (UC). Using LPS/ATP-stimulated human colonic epithelial cells (HCoEpiC) and dextran sulfate sodium (DSS)-induced mice, hydrogen-rich medium or hydrogen-rich water was administered. Hydrogen restored cell viability and reduced inflammatory cytokine release in HCoEpiC cells, while in mice it diminished intestinal injury, inflammation, pyroptosis, and NLRP3 inflammasome activation. Colon tissue from UC patients showed reduced PKM2 lactylation compared with healthy controls, and hydrogen administration elevated PKM2 lactylation without altering total PKM2 protein levels. The lactylation inhibitor sodium oxamate abolished these protective effects. Co-immunoprecipitation confirmed that lactylated PKM2 binds NLRP3, thereby dampening inflammasome assembly. Disruption of PKM2 lactylation eliminated this protein–protein interaction. Structural modeling further supported the binding interface between lactylated PKM2 and NLRP3. These findings indicate that hydrogen-mediated promotion of PKM2 lactylation is a key mechanism restraining NLRP3-driven pyroptosis and intestinal inflammation in UC.

### Mechanism

Molecular hydrogen enhances lactylation of PKM2, enabling lactylated PKM2 to directly bind NLRP3 and inhibit inflammasome assembly, thereby suppressing pyroptosis and downstream inflammatory cytokine production in colonic epithelial cells.

## Bibliographic

- **Authors**: Yang T, Lu FJ, Kang YN, Wang L, Li M, Xu W, et al.
- **Journal**: Int Immunopharmacol
- **Year**: 2026 (2026-07-01)
- **PMID**: [42035551](https://pubmed.ncbi.nlm.nih.gov/42035551/)
- **DOI**: [10.1016/j.intimp.2026.116726](https://doi.org/10.1016/j.intimp.2026.116726)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident 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)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 42035551. https://h2-papers.org/en/papers/42035551
> **Source**: PubMed PMID [42035551](https://pubmed.ncbi.nlm.nih.gov/42035551/)