Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Baltimore, Maryland.
Cancer Discov. 2022 Aug 5;12(8):1873-1885. doi: 10.1158/2159-8290.CD-21-1273.
Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient-derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients.
Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis. See related commentary by Jain and Dudeja, p. 1838. This article is highlighted in the In This Issue feature, p. 1825.
定义微生物组在结直肠癌中的复杂作用，以及发现新的、促肿瘤微生物，是目前积极研究的领域。在本研究中，培养和再关联实验表明，产毒艰难梭菌菌株在无特定病原体 ApcMin/+ 小鼠中驱动了一部分结直肠癌患者黏膜糊剂的肿瘤表型。肿瘤发生依赖于艰难梭菌毒素 TcdB，并与 Wnt 信号、活性氧和促肿瘤黏膜免疫反应有关，这些反应的特征是激活的髓样细胞浸润和产生 IL17 的淋巴和固有淋巴样细胞亚群。这些发现表明，与产毒艰难梭菌的慢性定植可能是患者结直肠癌的一个潜在驱动因素。
结直肠癌是全世界癌症和癌症相关死亡的主要原因，其病因是多因素的，可能包括促癌细菌。本研究使用人类结肠癌标本、培养和小鼠模型，证明了肠道病原体艰难梭菌的慢性感染是结肠肿瘤发生的一个以前未被认识到的因素。见 Jain 和 Dudeja 的相关评论，第 1838 页。本文在本期特色栏目中重点介绍，第 1825 页。
