<i>Streptococcus gallolyticus</i> subsp. <i>gallolyticus</i> promotes colorectal tumor development

<div><p><i>Streptococcus gallolyticus</i> subsp. <i>gallolyticus</i> (<i>Sg</i>) has long been known to have a strong association with colorectal cancer (CRC). This knowledge has important clinical implications, and yet little is known about the role of <i>Sg</i> in the development of CRC. Here we demonstrate that <i>Sg</i> promotes human colon cancer cell proliferation in a manner that depends on cell context, bacterial growth phase and direct contact between bacteria and colon cancer cells. In addition, we observed increased level of β-catenin, c-Myc and PCNA in colon cancer cells following incubation with <i>Sg</i>. Knockdown or inhibition of β-catenin abolished the effect of <i>Sg</i>. Furthermore, mice administered with <i>Sg</i> had significantly more tumors, higher tumor burden and dysplasia grade, and increased cell proliferation and β-catenin staining in colonic crypts compared to mice receiving control bacteria. Finally, we showed that <i>Sg</i> is present in the majority of CRC patients and is preferentially associated with tumor compared to normal tissues obtained from CRC patients. These results taken together establish for the first time a tumor-promoting role of <i>Sg</i> that involves specific bacterial and host factors and have important clinical implications.</p>