Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria
Increased Epithelial Oxygenation Links Colitis to an Expansion of Tumorigenic Bacteria
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DOI：
10.1128/mbio.02244-19
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发表时间：
2019-09-01
期刊：
影响因子：
6.4
通讯作者：
Baumler, Andreas J.
中科院分区：
文献类型：
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作者：
Cevallos, Stephanie A.;Lee, Jee-Yon;Baumler, Andreas J.
肠道炎症是结直肠癌形成的一个危险因素，但其潜在机制尚不清楚。在这里，我们研究了结肠炎是否会改变结肠微生物群以增强其致癌活性。结肠炎增加小鼠结肠上皮氧合，并通过有氧呼吸推动肠道相关微生物群落中大肠杆菌的扩张。在结肠炎相关结直肠癌形成的小鼠模型中，产生大肠杆菌素的大肠杆菌的有氧扩张是这种病原体诱导癌症活性所必需的。我们得出结论，结肠上皮氧合的增加与致癌驱动物种的扩张有关，从而增加了微生物群的致癌活性。肠道微生物群是结直肠癌形成的重要环境因素之一，但控制其致癌活性的栖息地过滤器尚不清楚。在这里，我们发现化学诱导的结肠炎提高了结肠上皮的氧合，从而推动了大肠杆菌素产生大肠杆菌的大肠杆菌的扩张，大肠杆菌是一种原癌驱动物种。这些数据表明，上皮氧合升高是结直肠癌形成的潜在危险因素，因为肠道栖息地的随之变化会加剧微生物群的致癌活性。
Intestinal inflammation is a risk factor for colorectal cancer formation, but the underlying mechanisms remain unknown. Here, we investigated whether colitis alters the colonic microbiota to enhance its cancer-inducing activity. Colitis increased epithelial oxygenation in the colon of mice and drove an expansion of Escherichia coli within the gut-associated microbial community through aerobic respiration. An aerobic expansion of colibactin-producing E. coli was required for the cancer-inducing activity of this pathobiont in a mouse model of colitis-associated colorectal cancer formation. We conclude that increased epithelial oxygenation in the colon is associated with an expansion of a prooncogenic driver species, thereby increasing the cancer-inducing activity of the microbiota.IMPORTANCE One of the environmental factors important for colorectal cancer formation is the gut microbiota, but the habitat filters that control its cancer-inducing activity remain unknown. Here, we show that chemically induced colitis elevates epithelial oxygenation in the colon, thereby driving an expansion of colibactinproducing Escherichia coli, a prooncogenic driver species. These data suggest that elevated epithelial oxygenation is a potential risk factor for colorectal cancer formation because the consequent changes in the gut habitat escalate the cancer-nducing activity of the microbiota.