<i>Akkermansia muciniphila</i> administration exacerbated the development of colitis-associated colorectal cancer in mice

Abstract

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. <i>Akkermansia mucinipila</i> is an important gram-negative anaerobic bacterium that can degrade mucin in gut. Previous studies suggested that <i>A. muciniphila</i> may affect inflammation and cell proliferation, but the relationship between <i>A. muciniphila</i> and CRC is not clarified. Here C57BL/6 mice were administrated with <i>A. muciniphila</i> or PBS and then treated with azoxymethane (AOM)/dextran sodium sulphate (DSS) to induce CRC. The mice receiving <i>A. muciniphila</i> 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 <i>A. muciniphila</i> treated mice. Furthermore, <i>A. muciniphila</i> administration induced more Ki67⁺ proliferating cells, higher PCNA expression and elevated gene expression of proliferation-associated molecules including <i>Snrpd1</i>, <i>Dbf4</i> or <i>S100A9</i>. At early stage of CRC development, in comparison with controls, the mice receiving <i>A. muciniphila</i> administration also had more body weight loss and shorter colon length, as well as higher gene expression of inflammatory cytokines. Furthermore, the <i>in vitro</i> experimental results showed that the co-culture of colon epithelial cells with <i>A. muciniphila</i> enhanced the cell proliferation and gene expression of proliferation-associated molecules. Therefore, <i>A. mucinipila</i> may promote the formation of CRC in mice through increasing the early level of inflammation and the proliferation of intestinal epithelial cells.