A Functional Food Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Inflammatory Colorectal Cancer in Mice

Jie Zhang; Zhewen Chen; Yanwen Lu; Daoyuan Tu; Fengqian Zou; Shouwen Lin; Weinan Yu; Mingyong Miao; Hanping Shi

doi:10.2147/OTT.S283465

A Functional Food Inhibits Azoxymethane/Dextran Sulfate Sodium-Induced Inflammatory Colorectal Cancer in Mice

Onco Targets Ther. 2021 Feb 26:14:1465-1477. doi: 10.2147/OTT.S283465. eCollection 2021.

Authors

Jie Zhang^#¹, Zhewen Chen^#², Yanwen Lu¹, Daoyuan Tu³, Fengqian Zou⁴, Shouwen Lin⁵, Weinan Yu¹, Mingyong Miao⁶, Hanping Shi⁷

Affiliations

¹ Department of Endocrinology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223002, Jiangsu, People's Republic of China.
² Department of Nutrition, Zhejiang Provincial People's Hospital, Hangzhou, 310000, Zhejiang, People's Republic of China.
³ Department of Gastrointestinal Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, 223002, Jiangsu, People's Republic of China.
⁴ Department of Academic, Yantai Briteley Institute of Life Sciences, Yantai, 264003, Shandong, People's Republic of China.
⁵ Center of Research and Development, Yantai Briteley Institute of Life Sciences, Yantai, 264003, Shandong, People's Republic of China.
⁶ Department of Biochemistry and Molecular Biology, The Naval Medical University, Shanghai, 200433, People's Republic of China.
⁷ Department of Gastrointestinal Surgery, Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: This study aimed to investigate the potential antitumor effects and mechanisms underlying the action of a functional food containing 55 different natural food ingredients.

Materials and methods: Azoxymethane/dextran sulfate sodium was used to establish a mouse model of colorectal cancer. Serum levels of cytokines, diamine oxidase, D-lactate, and endotoxin were measured using enzyme-linked immunosorbent assays. Immune cells from the mouse spleen and tumor tissue were analyzed by flow cytometry. Finally, 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were used to study the fecal microbiota and microbial metabolites, respectively.

Results: The tumor growth was significantly lower in the FFD group than in the model group. The intestinal barrier function, fat mass, and lean body mass were significantly improved in the FFD group compared with the model group. The levels of interleukin-6 and tumor necrosis factor-α were significantly lower in the FFD group, while the proportions of total T cells, CD3⁺CD4⁺, CD3⁺CD8⁺, and interferon-γ-producing CD4⁺ T cells were significantly higher. Analysis of the diversity of the gut microbiota identified 60 differential bacterial genera between the FFD and model groups, with lower abundances of Desulfovibrio and unclassified Ruminococcaceae and higher abundances of the beneficial bacterial genera Bacteroides and Parasutterella in the FFD group. The fecal metabolite analysis revealed 635 differential metabolites between the FFD and model groups, with lower levels of deuteroporphyrin IX and citrulline and higher levels of acetic acid and ascorbic acid in the FFD group.

Conclusion: Our results demonstrate that the functional food tested can inhibit the growth of colorectal cancer. This effect may be due to the ability of this food to improve nutritional status, enhance intestinal barrier function, and regulate the tumor microenvironment via changes in the intestinal microbiota and metabolites.

Keywords: cancer nutrition; colorectal cancer; functional food; gut microbiota; metabolite; tumor microenvironment.

Grants and funding

This study was supported by the National Key Research and Development Program: The key technology of palliative care and nursing for cancer patients (2017YFC1309200).