Hydrogen: An Endogenous Regulator of Liver Homeostasis

Abstract

Basic and clinical studies have shown that hydrogen (H₂), the lightest gas in the air, has significant biological effects of anti-oxidation, anti-inflammation, and anti-apoptosis. The mammalian cells have no abilities to produce H₂ due to lack of the expression of hydrogenase. The endogenous H₂ in human body is mainly produced by anaerobic bacteria, such as Firmicutes and Bacteroides, in gut and other organs through the reversible oxidation reaction of 2 H⁺ + 2 e^- ⇌ H₂. Supplement of exogenous H₂ can improve many kinds of liver injuries, modulate glucose and lipids metabolism in animal models or in human beings. Moreover, hepatic glycogen has strong ability to accumulate H₂, thus, among the organs examined, liver has the highest concentration of H₂ after supplement of exogenous H₂ by various strategies in vivo. The inadequate production of endogenous H₂ play essential roles in brain, heart, and liver disorders, while enhanced endogenous H₂ production may improve hepatitis, hepatic ischemia and reperfusion injury, liver regeneration, and hepatic steatosis. Therefore, the endogenous H₂ may play essential roles in maintaining liver homeostasis.

Keywords: apoptosis; glucose homeostasis; gut microbiota; inflammation; lipids homeostasis; oxidative stress.

Figure 1

The model of endogenous H₂ in modulating liver homeostasis. The endogenous H₂ is primarily produced by hydrogenase-expressing fermentative bacteria in the gastrointestinal tract. Moreover, H₂S and CH₄ are by-products of H₂ metabolism derived from sulphate-reducing bacteria and methanogenic bacteria, respectively. It should be noticed that hepatocyte can also produce H₂S and CH₄. The colonic gas mixture, including H_2, H₂S, CH₄, and other bioactive gas molecules produced by gut microbiota, can arrive at the liver by free diffusion or by blood circulation. These gas molecules may influence hepatic redox homeostasis, glucose and lipids homeostasis, immune and inflammatory homeostasis, respectively, together by another one or more. Therefore, H₂ may act as a novel bridge between gut and liver, and play a central role among the colonic gas mixture in modulating liver homeostasis.