Department of Biomedical Engineering, Texas A&M University, USA.
Artie McFerrin Department of Chemical Engineering, Texas A&M University, USA.
Lab Chip. 2024 Jul 23;24(15):3690-3703. doi: 10.1039/d4lc00013g.
Changes in the abundance of certain bacterial species within the colorectal microbiota correlate with colorectal cancer (CRC) development. While carcinogenic mechanisms of single pathogenic bacteria have been characterized , limited tools are available to investigate interactions between pathogenic bacteria and both commensal microbiota and colonocytes in a physiologically relevant tumor microenvironment. To address this, we developed a microfluidic device that can be used to co-culture colonocyte spheroids and colorectal microbiota. The device was used to explore the effect of , an opportunistic pathogen associated with colorectal cancer development in humans, on colonocyte gene expression and microbiota composition. altered the transcription of genes involved in cytokine production, epithelial-to-mesenchymal transition, and proliferation in colonocytes in a contact-independent manner; however, most of these effects were significantly diminished by the presence of commensal microbiota. Interestingly, significantly altered the abundance of multiple bacterial clades associated with mucosal immune responses and cancer development in the colon. Our results highlight the importance of evaluating the potential carcinogenic activity of pathogens in the context of a commensal microbiota, and the potential to discover novel inter-species microbial interactions in the CRC microenvironment.
结直肠微生物群中某些细菌种类丰度的变化与结直肠癌（CRC）的发展相关。虽然已经对单一致病菌的致癌机制进行了描述，但缺乏有效的工具来研究致病菌与共生菌群以及在生理相关的肿瘤微环境中的结肠细胞之间的相互作用。为了解决这个问题，我们开发了一种微流控装置，可用于共培养结肠细胞球体和结直肠微生物群。该装置用于研究与人类结直肠癌发展相关的机会致病菌 对结肠细胞基因表达和微生物群落组成的影响。以非接触方式改变了结肠细胞中细胞因子产生、上皮-间充质转化和增殖相关基因的转录；然而，共生菌群的存在显著降低了这些影响中的大多数。有趣的是，显著改变了与结直肠黏膜免疫反应和癌症发展相关的多个细菌类群的丰度。我们的研究结果强调了在共生菌群背景下评估病原体潜在致癌活性的重要性，以及在 CRC 微环境中发现新的种间微生物相互作用的潜力。
