产毒素的艰难梭菌,可在小鼠中促结肠肿瘤
创作:圆圈儿 审核:mildbreeze 07月01日
  • 不同结直肠癌患者的黏膜浆液在易患肠癌的Apc小鼠中有不同的致瘤能力;
  • 菌群分析、分离培养结合实验数据表明,患者黏膜浆液中的艰难梭菌产毒菌株可诱发小鼠的结肠肿瘤,其促瘤作用依赖于菌株的持续定植及产生的毒素TcdB;
  • 单细胞测序和流式分析表明,艰难梭菌诱导的肿瘤发生与肠上皮祖细胞Wnt信号活化、肠细胞活性氧生成以及促瘤性黏膜免疫反应(如活化髓系细胞的浸润、产IL-17淋巴细胞亚群增多)有关。
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mildbreeze
结直肠癌(CRC)的病因包括致癌细菌等多种因素。确定肠道菌群在CRC中的复杂作用、发现新的促瘤微生物,有助于更好地理解并治疗CRC。Cancer Discovery近期发表的这项研究,利用人类CRC标本、细菌分离培养、小鼠实验和测序等方法,首次证明肠道病原菌艰难梭菌产毒菌株的慢性感染,是诱发CRC的潜在因素。
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Cancer Discovery [IF:38.272]

Human colon cancer-derived Clostridioides difficile strains drive colonic tumorigenesis in mice

来自结肠癌患者的艰难梭菌毒株驱动小鼠的结肠肿瘤发生

10.1158/2159-8290.CD-21-1273

06-09, Article

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Defining the complex role of the microbiome in colorectal cancer (CRC) and the discovery of novel, pro-tumorigenic 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 CRC 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 pro-tumorigenic mucosal immune responses marked by infiltration of activated myeloid cells and interleukin-17 (IL-17)-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of CRC in patients.

First Authors:
Julia L Drewes,Jie Chen,Nicholas O Markham

Correspondence Authors:
Cynthia L Sears

All Authors:
Julia L Drewes,Jie Chen,Nicholas O Markham,Reece J Knippel,Jada C Domingue,Ada J Tam,June L Chan,Lana Kim,Madison McMann,Courtney Stevens,Christine M Dejea,Sarah Tomkovich,John Michel,James R White,Fuad Mohammad,Victoria L Campodonico,Cody N Heiser,Xinqun Wu,Shaoguang Wu,Hua Ding,Patricia Simner,Karen Carroll,Martha J Shrubsole,Robert A Anders,Seth T Walk,Christian Jobin,Fengyi Wan,Robert J Coffey,Franck Housseau,Ken S Lau,Cynthia L Sears

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