Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial steps that explain how CRC favors SGG colonization. By using mice genetically prone to CRC, we show that SGG colonization is 1,000-fold higher in tumor-bearing mice than in normal mice. This selective advantage occurs at the expense of resident intestinal enterococci. An SGG-specific locus encoding a bacteriocin (“gallocin”) is shown to kill enterococci in vitro. Importantly, bile acids strongly enhance this bacteriocin activity in vivo, leading to greater SGG colonization. Constitutive activation of the Wnt pathway, one of the earliest signaling alterations in CRC, and the decreased expression of the bile acid apical transporter gene Slc10A2, as an effect of the Apc founding mutation, may thereby sustain intestinal colonization by SGG. We conclude that CRC-specific conditions promote SGG colonization of the gut by replacing commensal enterococci in their niche.

中文翻译：

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大肠癌的特定条件促进解链球菌肠道定植

溶菌链球菌亚种定殖。溶脂菌（SGG）与大肠癌（CRC）的发生密切相关。但是，导致其成功定殖的因素尚不清楚，SGG是否会影响致癌过程或受益于容易发生肿瘤的环境仍是一个悬而未决的问题。在这里，我们阐明了关键步骤，这些步骤解释了CRC如何支持SGG定植。通过使用遗传上容易发生CRC的小鼠，我们显示出SGG定植在荷瘤小鼠中比正常小鼠高1000倍。这种选择性优势的产生是以居民肠道小肠球菌为代价的。显示了编码细菌素（“ gallocin”）的SGG特异性基因座在体外杀死肠球菌。重要的是，胆汁酸在体内强烈增强了这种细菌素的活性，从而导致更大的SGG定植。Wnt途径的组成性激活，Slc10A2，作为Apc建立突变的一种作用，可以因此通过SGG维持肠道定植。我们得出的结论是，CRC特定的条件通过替换其肠壁中的共肠球菌而促进了肠道SGG的定植。