Hydrogen Protects Gut Barrier from Sepsis-Related Damage in Lab Study
- Authors
- Tao Yang, Lu Wang, Ruiqiang Sun, Hongguang Chen, Hongtao Zhang, Yang Yu, Yanyan Wang, Guolin Wang, Yonghao Yu, Ke-Liang Xie
- Journal
- Shock
- Year
- 2016
- DOI
- 10.1097/SHK.0000000000000503
- Study Type
- Cell Culture
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Gastrointestinal
TL;DR
Breathing in hydrogen gas can help fix leakiness in the gut caused by severe infection, possibly by affecting certain cellular pathways.
Key Finding
Hydrogen-rich medium protected intestinal cells from lipopolysaccharide-induced barrier damage by activating a cellular pathway (RhoA-mDia1) that strengthens the connections between cells.
Summary
This laboratory study tested whether hydrogen-rich liquid could protect intestinal cells from damage caused by lipopolysaccharide (a bacterial toxin that triggers inflammation). Researchers grew human intestinal cells in dishes and exposed them to the toxin with or without hydrogen-rich medium. They found that hydrogen reduced the toxin's damaging effects by strengthening the cell barrier and reducing harmful molecules called free radicals, working through a specific cellular signaling pathway called RhoA-mDia1.
Practical Takeaway
While this cell culture study suggests hydrogen may help protect the intestinal barrier during severe infection or inflammation, it is very early-stage research conducted in a laboratory dish, not in humans or animals. Much more research would be needed before drawing any conclusions about whether hydrogen water could help people with sepsis or gut barrier problems.
Abstract
Gastrointestinal barrier dysfunction is associated with the severity and prognosis of sepsis. Hydrogen gas (H2) can ameliorate multiple organ damage in septic animals. Ras homolog gene family member A (RhoA) and mammalian diaphanous-related formin 1 (mDia1) are important to regulate tight junction (TJ) and adherens junction (AJ), both of which determine the integrity of the intestinal barrier. This study was aimed to investigate whether H2 could modulate lipopolysaccharide (LPS)-stimulated dysfunction of the intestinal barrier and whether RhoA-mDia1 signaling is involved. Caco-2 cells were exposed to different concentrations of LPS (1 μg/mL-1 mg/mL). The permeability of the intestinal barrier was evaluated by transepithelial resistance (TER) and fluorescein-isothiocyanate-dextran flux. Expression and distribution of occludin and E-cadherin were analyzed by Western blot and immunofluorescence. RhoA activity was measured by G-Lisa assay, and mDia1 expression was assessed by Western blot. LPS (100 μg/mL) decreased TER and increased fluorescein-isothiocyanate-dextran flux, which were alleviated by H2-rich medium. Also, H2 down-regulated LPS-induced oxidative stress. Moreover, H2 improved the down-regulated expression and redistribution of occludin and E-cadherin caused by LPS. Additionally, H2 alleviated LPS-caused RhoA activation, and the beneficial effects of H2 on barrier were counteracted by RhoA agonist CN03. Rho inhibitor C3 exoenzyme mitigated LPS-induced barrier breakdown. Furthermore, H2-rich medium increased mDia1 expression, and mDia1 knockdown abolished protections of H2 on barrier permeability. mDia1 knockdown eliminated H2-induced benefits for occludin and E-cadherin. These findings suggest that H2 improves LPS-induced hyperpermeability of the intestinal barrier and disruptions of TJ and AJ by moderating RhoA-mDia1 signaling.