Hydrogen-Rich Saline Regulates Intestinal Barrier Dysfunction, Dysbiosis, and Bacterial Translocation in a Murine Model of Sepsis

Abstract

Bacterial translocation is a major cause of multiple organ dysfunction syndrome in critical illness, and its management is an important therapeutic strategy. In this study, we focused on the key factors responsible for bacterial translocation including the intestinal microbiome and investigated the impact of molecular hydrogen therapy as a countermeasure against bacterial translocation in a murine model of sepsis. The experimental protocols were divided into the sham, saline treatment (control), and hydrogen treatment (H2) groups. In the H2 group, 15 mL/kg of hydrogen-rich saline (7 ppm) was gavaged daily for 7 days following cecal ligation and puncture (CLP). In the control group, normal saline was gavaged in the same way. In the results, the 7-day survival rate was significantly improved in the H2 group versus the control group (69% vs. 31%, P < 0.05). The incidence of bacterial translocation at 24 h after CLP as assessed by cultivation of mesenteric lymph nodes and blood was significantly decreased in the H2 group versus the control group. Administration of hydrogen-rich saline also prevented the expansion of facultative anaerobic Enterobacteriaceae and ameliorated intestinal hyperpermeability at 24 h after CLP. Intestinal tissue levels of inflammatory mediators such as inducible nitric oxide synthases, tumor necrosis factor α, interleukin (IL)-1β, IL-6, and oxidative stress marker malondialdehyde at 6 h after CLP were down-regulated in the H2 group. These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.

Hydrogen-rich saline protects intestinal epithelial tight junction barrier in rats with intestinal ischemia–reperfusion injury by inhibiting endoplasmic reticulum stress-induced apoptosis pathway

“…In this study, HRS decreased the Chiu score and the expression levels of serum IFABP, TNFα and IL-1β, which indicated that HRS could alleviate the intestinal epithelial cells injury within hours after ischemia-reperfusion. Ikeda et al have found that there were no significant differences between the control and H 2 groups in the analysis of mRNA expression of tight junction proteins ZO-1 and occludin at 24 h after cecal ligation and puncture [43]. In our study, however, compared with the I/R group, the application of HRS could maintain the expression levels of intestinal epithelial TJ proteins occludin and ZO-1.…”

<p>iTRAQ-Based Quantitative Proteomic Analysis of Intestines in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment</p>

“…21 Studies have confirmed that hydrogen-rich saline can regulate intestinal barrier dysfunction and bacterial migration in mouse models of sepsis. 22 Previous studies have shown that the loss of barrier function of intestinal epithelial cells may be caused by the destruction of epithelial cells and severe metabolic injury caused by sepsis. 23 These effects may be related to the disturbance of intestinal microbiota after sepsis.…”

The gut microbiome’s role in the development, maintenance, and outcomes of sepsis

“…Animal studies have demonstrated conflicting results regarding specific inflammatory pathways, reflecting the complexity of the relationship between the gut microbiome and the immune system. For example, in a mouse model of Streptococcus pneumoniae sepsis, pre-treatment with oral antibiotics prior to sepsis onset was associated with lower levels of lung TNF-α, a pro-inflammatory cytokine [25], whereas others have shown the opposite effect of gut microbiome depletion on TNF-α [21,22,[37][38][39]. Despite differences in specific cytokine expression between studies, the overall effect of alteration of normal gut microbiome structure prior to sepsis onset appears to be a more robust inflammatory response to sepsis [21,22,25,[37][38][39][40][41].…”