Hydrogen peroxide production by lactobacilli promotes epithelial restitution during colitis

Ashish K. Singh, Rosanne Y. Hertzberger, Ulla G. Knaus*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disease of the gastrointestinal tract, characterized by cycles of acute flares, recovery and remission phases. Treatments for accelerating tissue restitution and prolonging remission are scarce, but altering the microbiota composition to promote intestinal homeostasis is considered a safe, economic and promising approach. Although probiotic bacteria have not yet fulfilled fully their promise in clinical trials, understanding the mechanism of how they exert beneficial effects will permit devising improved therapeutic strategies. Here we probe if one of the defining features of lactobacilli, the ability to generate nanomolar H2O2, contributes to their beneficial role in colitis. H2O2 generation by wild type L. johnsonii was modified by either deleting or overexpressing the enzymatic H2O2 source(s) followed by orally administering the bacteria before and during DSS colitis. Boosting luminal H2O2 concentrations within a physiological range accelerated recovery from colitis, while significantly exceeding this H2O2 level triggered bacteraemia. This study supports a role for increasing H2O2 within the physiological range at the epithelial barrier, independently of the enzymatic source and/or delivery mechanism, for inducing recovery and remission in IBD.

Original languageEnglish
Pages (from-to)11-20
Number of pages10
JournalRedox Biology
Volume16
Issue numberJune
Early online date12 Feb 2018
DOIs
Publication statusPublished - Jun 2018

Funding

We thank G. Aviello for advice and support; B. Bourke and staff at National Children Research Centre, Our Lady's Hospital for Children Crumlin for providing equipment and histology support. We acknowledge D. Pridmore (previously at Nestlé Research Center, Vers-Chez-Les-Blanc, Switzerland) for preparation of the deletion mutant and overexpression plasmid. We thank S. Duboux (Nestlé Research Center) for facilitating transfer of the deletion strain and plasmid. This work was supported by Science Foundation Ireland and by the National Childrens Research Center (UGK). AKS was partially supported by an Erasmus Mundus Research Mobility Fellowship funded by The European Union. Appendix A

FundersFunder number
National Childrens Research Center
UGK
European Commission
Science Foundation Ireland

    Keywords

    • DSS colitis
    • Hydrogen peroxide
    • Inflammatory bowel disease
    • Lactobacilli
    • Mucosal healing
    • Tissue restitution

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