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Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis

1
Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
2
Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, China
3
Oncology Pathology, Department of Pathology and Host-Defence, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrea Fabbri
Nutrients 2022, 14(3), 649; https://doi.org/10.3390/nu14030649
Received: 9 January 2022 / Revised: 27 January 2022 / Accepted: 29 January 2022 / Published: 3 February 2022
(This article belongs to the Section Nutrition and Metabolism)
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. View Full-Text
Keywords: inflammatory bowel disease; colorectal cancer; lactulose; gut microbiota inflammatory bowel disease; colorectal cancer; lactulose; gut microbiota
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MDPI and ACS Style

Hiraishi, K.; Zhao, F.; Kurahara, L.-H.; Li, X.; Yamashita, T.; Hashimoto, T.; Matsuda, Y.; Sun, Z.; Zhang, H.; Hirano, K. Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis. Nutrients 2022, 14, 649. https://doi.org/10.3390/nu14030649

AMA Style

Hiraishi K, Zhao F, Kurahara L-H, Li X, Yamashita T, Hashimoto T, Matsuda Y, Sun Z, Zhang H, Hirano K. Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis. Nutrients. 2022; 14(3):649. https://doi.org/10.3390/nu14030649

Chicago/Turabian Style

Hiraishi, Keizo, Feiyan Zhao, Lin-Hai Kurahara, Xiaodong Li, Tetsuo Yamashita, Takeshi Hashimoto, Yoko Matsuda, Zhihong Sun, Heping Zhang, and Katsuya Hirano. 2022. "Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis" Nutrients 14, no. 3: 649. https://doi.org/10.3390/nu14030649

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