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

Ikeda, Mitsunori*; Shimizu, Kentaro*; Ogura, Hiroshi*; Kurakawa, Takashi; Umemoto, Eiji; Motooka, Daisuke; Nakamura, Shota; Ichimaru, Naotsugu§; Takeda, Kiyoshi; Takahara, Shiro§; Hirano, Shin-ichi||; Shimazu, Takeshi*

doi: 10.1097/SHK.0000000000001098
Basic Science Aspects
Editor's Choice

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.

*Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan

Department of Infection Metagenomics, Research Institute for Microbial Disease, Osaka University Graduate School of Medicine, Osaka, Japan

§Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan

||MiZ Co, Ltd, Kanagawa, Japan

Address reprint requests to Mitsunori Ikeda, MD, Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan; E-mail: mitsurf109@hp-emerg.med.osaka-u.ac.jp

Received 5 October, 2017

Revised 22 October, 2017

Accepted 21 December, 2017

NI and ST declare that they belong to the endowed course, and there is no conflict of interest that could be perceived as prejudicing the impartiality of this article.

MI participated in the study design, interpretation, and statistical analysis and drafted the article. KS participated in the analysis of the data. TK, EU, DM, and SN made critical contributions to the development of this study and helped in drafting the article. HO, NI, KT, ST, SH, and TS supervised the study and revised the article. All authors read and approved the final version.

The authors report no conflicts of interest.

© 2018 by the Shock Society