Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice.
Akkermansia muciniphila administration exacerbated the development of colitis-associated colorectal cancer in mice.
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DOI：
10.7150/jca.63578
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发表时间：
2022
影响因子：
3.9
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Wang F;Cai K;Xiao Q;He L;Xie L;Liu Z
结直肠癌是最常见的消化道恶性肿瘤之一，炎症和肠道菌群是影响结直肠癌发生的关键因素。粘蛋白阿克曼氏菌（Akkermansia mucinipila）是一种重要的革兰氏阴性厌氧细菌，能降解肠道粘蛋白。以往的研究表明，A. muciniphila可能影响炎症和细胞增殖，但A.嗜粘蛋白菌和CRC未阐明。在此，C57 BL/6小鼠被给予A.用嗜粘蛋白菌或PBS处理，然后用氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）处理以诱导CRC。A.在AOM/DSS处理后，与接受PBS给药的那些相比，给予嗜粘蛋白的那些具有更严重的体重减轻、更短的结肠长度和更多的肠肿瘤。A组结肠损伤明显，杯状细胞减少。嗜粘蛋白体处理的小鼠。此外，A.给予muciniphila诱导更多的Ki 67+增殖细胞、更高的PCNA表达和包括Snrpd 1、Dbf 4或S100 A9的增殖相关分子的基因表达升高。在结直肠癌早期，与对照组相比，A.给予嗜粘蛋白的小鼠也具有更多的体重减轻和更短的结肠长度，以及更高的炎性细胞因子的基因表达。体外实验结果表明，结肠上皮细胞与A。muciniphila增强细胞增殖和增殖相关分子的基因表达。因此，A.粘蛋白质可能通过增加早期炎症水平和肠上皮细胞增殖促进小鼠结直肠癌的形成。
Colorectal cancer (CRC) is one of the most common digestive tract malignancies and inflammation and gut microbiota are well-known key factors to influence CRC development. Akkermansia mucinipila is an important gram-negative anaerobic bacterium that can degrade mucin in gut. Previous studies suggested that A. muciniphila may affect inflammation and cell proliferation, but the relationship between A. muciniphila and CRC is not clarified. Here C57BL/6 mice were administrated with A. muciniphila or PBS and then treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CRC. The mice receiving A. muciniphila administration had more serious weight loss, shorter colon length and more intestinal tumors than those receiving PBS administration after AOM/DSS treatment. More colon damage and less goblet cells were also observed in A. muciniphila treated mice. Furthermore, A. muciniphila administration induced more Ki67+ proliferating cells, higher PCNA expression and elevated gene expression of proliferation-associated molecules including Snrpd1, Dbf4 or S100A9. At early stage of CRC development, in comparison with controls, the mice receiving A. muciniphila administration also had more body weight loss and shorter colon length, as well as higher gene expression of inflammatory cytokines. Furthermore, the in vitro experimental results showed that the co-culture of colon epithelial cells with A. muciniphila enhanced the cell proliferation and gene expression of proliferation-associated molecules. Therefore, A. mucinipila may promote the formation of CRC in mice through increasing the early level of inflammation and the proliferation of intestinal epithelial cells.
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DOI：
10.1016/j.bbadis.2018.10.006
发表时间：
2018-12
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Howe C;Kim SJ;Mitchell J;Im E;Kim YS;Kim YS;Rhee SH
通讯作者：
Rhee SH
影响因子：
4.4
作者：
Ottman, Noora;Davids, Mark;de Vos, Willem M.
通讯作者：
de Vos, Willem M.
影响因子：
4.2
作者：
Mangin, I;Bonnet, R;Doré, J
通讯作者：
Doré, J
影响因子：
4
作者：
Chen J;Wang Z;Yu S
通讯作者：
Yu S
DOI：
10.1016/j.bpg.2017.10.001
发表时间：
2017-12-01
影响因子：
3.2
作者：
Ottman, Noora;Geerlings, Sharon Y.;Belzer, Clara
通讯作者：
Belzer, Clara