Lactulose mediates suppression of dextran sodium sulfate-induced colon inflammation by increasing hydrogen production

Dig Dis Sci. 2013 Jun;58(6):1560-8. doi: 10.1007/s10620-013-2563-7. Epub 2013 Jan 31.


Background: Molecular hydrogen (H2) is a potent antioxidant and able to protect organs from oxidative stress injuries. Orally administered lactulose, a potent H2 inducer, is digested by colon microflora and significantly increases H2 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, H2-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 H2 breath test was used to determine the exhaled H2 concentration. Body weight, colitis score, colon length, pathological features and tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), 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-α, IL-1β, MDA, and MPO in colon lesions, were significantly suppressed by oral lactulose administration and intraperitoneally injected H2-rich saline. Ingestion of antibiotics significantly compromised the anti-inflammatory effects of lactulose. The H2 breath test showed that lactulose administration significantly induced hydrogen production and that antibiotics administration could inhibit H2 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 H2 production.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Biomarkers / metabolism
  • Breath Tests
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / microbiology
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Dextran Sulfate
  • Drug Administration Schedule
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Agents / therapeutic use*
  • Hydrogen / metabolism
  • Lactulose / pharmacology
  • Lactulose / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Oxidative Stress / drug effects
  • Random Allocation


  • Anti-Bacterial Agents
  • Biomarkers
  • Gastrointestinal Agents
  • Lactulose
  • Hydrogen
  • Dextran Sulfate