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- Title
Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis.
- Authors
Hiraishi, Keizo; Zhao, Feiyan; Kurahara, Lin-Hai; Li, Xiaodong; Yamashita, Tetsuo; Hashimoto, Takeshi; Matsuda, Yoko; Sun, Zhihong; Zhang, Heping; Hirano, Katsuya
- Abstract
Lactulose, a galactose-fructose disaccharide, is made from the milk sugar lactose by heating or isomerization processes. Lactulose is proposed to modulate gut microbiota and thus expected to be beneficial in treating inflammatory bowel disease. In the present study, we investigated the therapeutic effect of lactulose on gastrointestinal inflammation and inflammation-related tumorigenesis in a mouse model of colorectal cancer as well as its effect on gut microbiota composition. Azoxymethane (AOM)/dextran sulfate sodium (DSS) model was used in this study. Lactulose treatment was performed by feeding 2% lactulose for 14 weeks. Stool samples collected at 4 time points were used for metagenomic analysis of the microbiota. Pathological analysis was performed 21 weeks after AOM injection. AOM/DSS increased the macrophage counts, inflammatory cytokine expression, colorectal tumorigenesis, and imbalance in gut microbiota composition, as evidenced by increased pathogen abundance (e.g., Escherichia and Clostridium). Lactulose significantly inhibited the inflammatory events, and ameliorated inflammation and tumorigenesis. The composition of the intestinal microbiota was also restored upon lactulose treatment, and lactulose reduced pathogen abundance and increased the abundance of Muribaculum and Lachnospiraceae. Meanwhile, the pathways related to Crohn's disease were downregulated after lactulose treatment. Our findings suggest that lactulose restores the structure and composition of the intestinal microbiota, mitigates inflammation, and suppresses inflammatory tumorigenesis.
- Subjects
CROHN'S disease; CYTOKINES; ESCHERICHIA coli; INFLAMMATORY bowel diseases; CARCINOGENS; GUT microbiome; CARCINOGENESIS; INFLAMMATION; ANIMAL experimentation; COLORECTAL cancer; FECES; COLITIS; MICE; DEXTRAN
- Publication
Nutrients, 2022, Vol 14, Issue 3, p649
- ISSN
2072-6643
- Publication type
Article
- DOI
10.3390/nu14030649