Hydrogen peroxide production by lactobacilli promotes epithelial restitution during colitis

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 H(2)O(2), contributes to their beneficial role in colitis. H(2)O(2) generation by wild type L. johnsonii was modified by either deleting or overexpressing the enzymatic H(2)O(2) source(s) followed by orally administering the bacteria before and during DSS colitis. Boosting luminal H(2)O(2) concentrations within a physiological range accelerated recovery from colitis, while significantly exceeding this H(2)O(2) level triggered bacteraemia. This study supports a role for increasing H(2)O(2) within the physiological range at the epithelial barrier, independently of the enzymatic source and/or delivery mechanism, for inducing recovery and remission in IBD.