Amending microbiota by targeting intestinal inflammation for colorectal cancer prevention (RNAseq)

We established the role of microbiota in mediating carcinogenesis blockade by anti-TNF therapy using chemically induced (DSS/Apcmin/+) and spontaneous (Apcmin/+;Il10-/-) mouse models of colitis-associated CRC. We found that in both models, TNF blockade attenuated inflammation and colibactin-producing E. coli (clb+ E. coli)-mediated CRC development. 16S rRNA gene sequencing and microbial RNA sequencing revealed significant microbiota structural and activity changes associated with disease development, which were prevented by TNF blockade.

本研究采用化学诱导型（DSS/Apcmin/+）与自发型（Apcmin/+;Il10-/-）结肠炎相关结直肠癌（colitis-associated CRC）小鼠模型，阐明了微生物群（microbiota）介导抗TNF治疗（anti-TNF therapy）发挥致癌阻断作用的机制。研究发现，在两类模型中，TNF阻断（TNF blockade）均可减轻炎症反应，并抑制产colibactin大肠杆菌（colibactin-producing E. coli，clb+ E. coli）介导的结直肠癌发生发展。通过16S rRNA基因测序（16S rRNA gene sequencing）与微生物转录组测序（microbial RNA sequencing）分析，本研究揭示了与疾病进展相关的微生物群结构与活性存在显著改变，而TNF阻断可有效阻止此类变化的发生。