Lactulose Mediates Suppression of Dextran Sodium Sulfate-Induced Colon Inflammation by Increasing Hydrogen Production

Background Molecular hydrogen (H-2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H-2 inducer, is digested by colon microflora and significantly increases H-2 production, indicating its potential anti-inflammatory action. Objective To evaluate the anti-inflammatory effects of lactulose on dextran sodium sulfate (DSS)-induced colitis in mice. Methods Mice were randomly assigned into seven groups, receiving regular distilled water, H-2-rich saline (peritoneal injection), DSS, oral lactulose (0.1, 0.15, 0.2 ml/10 g, respectively), and lactulose (0.2 ml/10 g) + oral antibiotics. The mouse model of human ulcerative colitis was established by supplying mice with water containing DSS. The H-2 breath test was used to determine the exhaled H-2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), maleic dialdehyde (MDA) and marrow peroxidase (MPO) levels in colon lesions were evaluated. Results After 7 days, DSS-induced loss of body weight, increase of colitis score, shortening of colon length, pathological changes and elevated levels of TNF-alpha, IL-1 beta, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H-2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H-2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H-2 production. Conclusion Lactulose can prevent the development of DSS-induced colitis and alleviate oxidative stress in the colon, as measured by MDA and MPO, probably by increasing endogenous H-2 production.