Oral glutathione supplementation drastically reduces Helicobacter-induced gastric pathologies.

Ellen De Bruyne,Richard Ducatelle,Dennis Foss,Bram Flahou,Myrthe Joosten,Frank Pasmans,Margaret Sanchez,Freddy Haesebrouck,Guangzhi Zhang,Annemieke Smet

doi:10.1038/srep20169

Ellen De Bruyne, Richard Ducatelle + Show 8 more

Open Access

https://doi.org/10.1038/srep20169

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Journal: Scientific Reports	Publication Date: Feb 2, 2016
Citations: 20	License type: CC BY 4.0

Affiliation: Ghent University, Zoetis (United States)

Abstract

Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known on the metabolism of this bacterium and its impact on the host. In this study, we have revealed the importance of the glutamate-generating metabolism, as shown by a complete depletion of glutamine (Gln) in the medium during H. suis culture. Besides Gln, H. suis can also convert glutathione (GSH) to glutamate, and both reactions are catalyzed by the H. suis γ-glutamyltranspeptidase (GGT). Both for H. pylori and H. suis, it has been hypothesized that the degradation of Gln and GSH may lead to a deficiency for the host, possibly initiating or promoting several pathologies. Therefore the in vivo effect of oral supplementation with Gln and GSH was assessed. Oral supplementation with Gln was shown to temper H. suis induced gastritis and epithelial (hyper)proliferation in Mongolian gerbils. Astonishingly, supplementation of the feed with GSH, another GGT substrate, resulted in inflammation and epithelial proliferation levels returning to baseline levels of uninfected controls. This indicates that Gln and GSH supplementation may help reducing tissue damage caused by Helicobacter infection in both humans and pigs, highlighting their potential as a supportive therapy during and after Helicobacter eradication therapy.

Highlights

Which leads to apoptosis or necrosis of gastric epithelial cells in vitro[15]
Since degradation of GSH and Gln by GGT from gastric helicobacters largely contribute to the glutamate-generating metabolism, we investigated the effect of GGT substrate supplementation (Gln/GSH) on the outcome of an experimental H. suis infection in Mongolian gerbils
Annotation of the H. suis genome identified no homologues for some important genes with a putative role in glucose metabolism[21], suggesting that H. suis is unable to utilize the glycolytic pathway for metabolism

Summary

Introduction

Which leads to apoptosis or necrosis of gastric epithelial cells in vitro[15]. Gln plays a crucial role in the energy supply of rapidly dividing cells, such as intestinal epithelial cells and cells of the immune system[23] This amino acid plays a role in protein turn-over and purine and pyrimidine synthesis[24,25]. The tripeptide GSH (γ-L-glutamyl-L-cysteinylglycine) is synthesized intracellularly This ubiquitous free thiol is important for anti− oxidative protection of the plasma membrane and organelles, but it plays distinct roles in cell cycle regulation and apoptosis[26,27]. The degradation products can be translocated into the cell, were they can for instance be recycled for GSH synthesis[28] Both deamination of Gln and degradation of GSH by Helicobacter GGT generate glutamate[15,16,20], which can be taken up in the bacterial cell by a Na+-dependent transporter[20,29]. By correcting for possible imbalances, we aimed at reducing infection-related gastric pathologies

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Conclusion