Abstract
Gut microbes play a crucial role in the development of colorectal cancer. Chitooligosaccharides (COS), are oligomer that are depolymerized from chitosan and possess a wide range of biological activities. In this study, the effects of COS on colorectal cancer (CRC) development were evaluated using azoxymethane and dextran sulfate sodium (AOM/DSS) induced mouse model of CRC (CACM). In the COS-treated CRC group (CMCOS), COS protected mice from CRC by decreasing the disease activity index, tumor incidences and multiplicity, and the mRNA levels of COX-2, IL-6, TNF-α, IL-1β, IL-10, and IKK-β mRNA in colonic epithelial cells. The results of a cage-exchanged experiment, in which mice from the CACMe and CMCOSe treatments exchanged cages every day to interact with microbes, showed that gut microbes play an important role in preventing CAC by COS. The abundances of fecal bacteria (total bacteria, Lactobacillus, Enterococcus, Fusobacterium nucleatum and butyrate-producing bacteria) were detected by qPCR on the 0th, 1st, 3rd, 6th, 9th, and 10th weekends. Furthermore, microbiota and mycobiota were analyzed by high-throughput sequencing on an Illumina MiSeq PE300 system. COS protected mice from CRC by reversing the imbalance of bacteria and fungi, especially by reducing the abundance of Escherichia–Shigella, Enterococcus, and Turicibacter, and increasing the levels of Akkermansia, butyrate-producing bacteria and Cladosporium.
Highlights
Colorectal cancer (CRC) is the third most common cause of cancer death in the world (GLOBOCON, 2012), accounting for approximately 862,000 deaths in 2018 (∼8.98% of total cancer-related deaths, respectively) (World Health Organization, 2018, Fact sheet 297)
Microbiota and Mycobiota in Colorectal Cancer be responsible for the development of colorectal cancer (CRC) including inheritance and environmental factors (Dulal and Keku, 2014)
Luan et al (2015) analyzed the fungal microbiota of biopsy samples from colorectal adenomas and adjacent tissues by sequencing and observed that fungal diversity was decreased in adenomas, while the size of adenomas and disease stage were closely related to changes in the mycobiota
Summary
Colorectal cancer (CRC) is the third most common cause of cancer death in the world (GLOBOCON, 2012), accounting for approximately 862,000 deaths in 2018 (∼8.98% of total cancer-related deaths, respectively) (World Health Organization, 2018, Fact sheet 297). Bacteria prevented the development of CRC by producing metabolites (e.g., acetate, propionate, and butyrate) (Louis et al, 2014). Due to their low levels in the gut (0.2%, 66 genera and 184 species), fungi are often ignored in studies of intestinal microbes. Because of its effects on modulating immunity, producing mycotoxins and interacting with microbiota (Van Raay and Allen-Vercoe, 2017), the role of mycobiota in the development and prevention of CRC should be further investigated. High-throughput sequencing was performed to reveal the structure of microbiota and mycobiota, and to determine the specific functional bacteria and fungi that contributed to the preventative effect of COS on CRC
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