[Background and purpose]
Lactulose is a non-digestible galactose-fructose disaccharide, which is clinically used for the treatment of chronic constipation and hepatic encephalopathy. This study is aimed to clarify the therapeutic effect of lactulose on the intestinal flora and colitis associated tumor formation in a colitis-associated tumor mouse model.
[Method]
Model mice were created by intraperitoneal administration of 12 mg/kg BW azoxymethane (AOM) followed by 3 sets of sodium dextran sulfate (DSS) treatment by feeding 2% DSS-containing drinking water for 7 days. The lactulose treatment was started after DSS treatment, by feeding 2% lactulose-containing chow for 14 weeks. The metagenome analysis of feces, histopathological analysis and inflammation-related analysis were performed 24 weeks after AOM administration.
[Result]
In the AOM / DSS model, the greater degree of intestinal inflammation, fibrosis and colorectal tumorigenesis as well as alteration of the structure of intestinal flora were observed compared to the normal group. The mRNA expression of TNF-α, IL-6, and TGF-β1 at non-tumor areas was upregulated. Lactulose treatment significantly improved the inflammation and tumorigenesis. Lactulose treatment restored the structure of intestinal flora, especially with respect to Bacteroides caecimurisLactobacillus intestinalis, and Lactobacillus murinus
[Discussion]
The suppression of inflammatory bowel tumor formation by lactulose correlates with improvement of the intestinal flora structure.