Intestinal inflammation and microbiota are two important components of colorectal cancer (CRC) etiology. However, it is not clear how tuning inflammation using clinically relevant anti-inflammatory treatment impacts microbiota or whether this consequently influences CRC outcome. Here, using chemically induced (DSS/Apc^min/+) and spontaneous (Apc^min/+;Il10^−/−) mouse CRC models colonized by colibactin-producing Escherichia coli, we established the role of microbiota in mediating the antitumorigenic effect of anti–tumor necrosis factor (TNF) therapy. We found that TNF blockade attenuated colitis and CRC development. Microbiota community structure and gene activities significantly changed with disease development, which was prevented by TNF blockade. Several microbiota functional pathways underwent similar changes in patients following anti-TNF therapy. Under cohousing condition, TNF blockade failed to prevent colitis, cancer development and disease-associated microbiota structural changes. Finally, microbiota transplantation showed reduced carcinogenic activity of microbiota from anti-TNF-treated mice. Together, our data demonstrate the plasticity of microbiota, which could be reverted to noncarcinogenic status by targeting inflammation.

肠道炎症和微生物群是结直肠癌 (CRC) 病因的两个重要组成部分。然而，尚不清楚使用临床相关的抗炎治疗来调节炎症如何影响微生物群，或者这是否会因此影响 CRC 结果。在这里，使用化学诱导 (DSS/ Apc ^min/+ ) 和自发 ( Apc ^min/+ ; Il10 ^-/- ) 小鼠 CRC 模型，该模型被产大肠杆菌素的大肠杆菌定殖，我们确定了微生物群在介导抗肿瘤坏死因子（TNF）治疗的抗肿瘤作用中的作用。我们发现 TNF 阻断可减轻结肠炎和 CRC 的发展。微生物群落结构和基因活动随着疾病的发展而发生显着变化，而 TNF 阻断可以防止这种变化。在接受抗 TNF 治疗的患者中，一些微生物群功能通路发生了类似的变化。在同居条件下，TNF 阻断未能预防结肠炎、癌症发展和与疾病相关的微生物群结构变化。最后，微生物群移植显示来自抗 TNF 治疗小鼠的微生物群的致癌活性降低。总之，我们的数据证明了微生物群的可塑性，可以通过靶向炎症将其恢复为非致癌状态。