Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis
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 e...
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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2072-6643/14/3/649 |
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| author | Keizo Hiraishi Feiyan Zhao Lin-Hai Kurahara Xiaodong Li Tetsuo Yamashita Takeshi Hashimoto Yoko Matsuda Zhihong Sun Heping Zhang Katsuya Hirano |
| author_facet | Keizo Hiraishi Feiyan Zhao Lin-Hai Kurahara Xiaodong Li Tetsuo Yamashita Takeshi Hashimoto Yoko Matsuda Zhihong Sun Heping Zhang Katsuya Hirano |
| author_sort | Keizo Hiraishi |
| collection | DOAJ |
| description | 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., <i>Escherichia</i> and <i>Clostridium</i>). 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 <i>Muribaculum</i> and <i>Lachnospirac</i><i>eae</i>. 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. |
| first_indexed | 2024-03-09T23:21:03Z |
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| last_indexed | 2024-03-09T23:21:03Z |
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| series | Nutrients |
| spelling | doaj.art-fe07f7762ba549b48b009ac93c8cc7232023-11-23T17:27:18ZengMDPI AGNutrients2072-66432022-02-0114364910.3390/nu14030649Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated TumorigenesisKeizo Hiraishi0Feiyan Zhao1Lin-Hai Kurahara2Xiaodong Li3Tetsuo Yamashita4Takeshi Hashimoto5Yoko Matsuda6Zhihong Sun7Heping Zhang8Katsuya Hirano9Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanKey Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, ChinaDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanOncology Pathology, Department of Pathology and Host-Defence, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanKey Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, ChinaKey Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot 010018, ChinaDepartment of Cardiovascular Physiology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, JapanLactulose, 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., <i>Escherichia</i> and <i>Clostridium</i>). 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 <i>Muribaculum</i> and <i>Lachnospirac</i><i>eae</i>. 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.https://www.mdpi.com/2072-6643/14/3/649inflammatory bowel diseasecolorectal cancerlactulosegut microbiota |
| spellingShingle | Keizo Hiraishi Feiyan Zhao Lin-Hai Kurahara Xiaodong Li Tetsuo Yamashita Takeshi Hashimoto Yoko Matsuda Zhihong Sun Heping Zhang Katsuya Hirano Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis Nutrients inflammatory bowel disease colorectal cancer lactulose gut microbiota |
| title | Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis |
| title_full | Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis |
| title_fullStr | Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis |
| title_full_unstemmed | Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis |
| title_short | Lactulose Modulates the Structure of Gut Microbiota and Alleviates Colitis-Associated Tumorigenesis |
| title_sort | lactulose modulates the structure of gut microbiota and alleviates colitis associated tumorigenesis |
| topic | inflammatory bowel disease colorectal cancer lactulose gut microbiota |
| url | https://www.mdpi.com/2072-6643/14/3/649 |
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