Hydrogen peroxide production by lactobacilli promotes epithelial restitution during colitis

• Published in: Redox biology 2018-06, Vol.16, p.11-20
• Main Authors: Singh, Ashish K., Hertzberger, Rosanne Y., Knaus, Ulla G.
• Format: Article
• Language: English
• Subjects: Animals; Colitis - chemically induced; Colitis - metabolism; Colitis - microbiology; Colitis - pathology; Dextran Sulfate - toxicity; Disease Models, Animal; DSS colitis; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene Expression Regulation; Humans; Hydrogen peroxide; Hydrogen Peroxide - isolation & purification; Hydrogen Peroxide - metabolism; Inflammatory bowel disease; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - microbiology; Inflammatory Bowel Diseases - pathology; Lactobacilli; Lactobacillus - metabolism; Mice; Mice, Inbred C57BL; Microbiota; Mucosal healing; Research Paper; Tissue restitution
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2018.02.003

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. [Display omitted] •Oral supplementation with Lactobacillus accelerated recovery from colitis.•H2O2 generation by L. johnsonii Nfr and Nox mediated intestinal tissue restitution.•Exceeding the physiological range of H2O2 induced bacteraemia in mice.•High dose antioxidants showed no benefit in an IBD mouse model.