Hong Yuntian, Chen Baoxiang, Zhai Xiang, Qian Qun, Gui Rui, Jiang Congqing
Department of Colorectal and Anal Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Clinical Center of Intestinal and Colorectal Diseases of Hubei Province, Wuhan, China.
Front Microbiol. 2023 Jan 13;13:1082835. doi: 10.3389/fmicb.2022.1082835. eCollection 2022.
Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including , , and . Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC.
结直肠癌（CRC）是全球常见的恶性肿瘤，肠道微生物群和代谢产物在其发生发展中起重要作用。在本研究中，我们构建了炎症诱导的结直肠肿瘤小鼠模型，采用固定剂量的氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）。我们发现，只有部分接受特定浓度AOM/DSS治疗的小鼠形成了结直肠肿瘤（肿瘤组），而其他小鼠未发生肿瘤（非肿瘤组）。进行了16S rDNA扩增子测序和液相色谱-质谱联用（LC-MS）/MS分析，以研究粪便样本中的微生物和代谢产物。结果，从粪便样本中获得了1189个可操作分类单元（OTU），非肿瘤组的OTU丰富度和多样性相对较高。此外，在门和属水平上鉴定出53种不同的微生物，包括 、 和 。此外，根据线性判别分析得分（log）>4，非肿瘤组有四种细菌类群明显富集。非靶向代谢组学分析揭示了粪便样本和代谢表型之间的显著差异。此外，热图和火山图分别显示了两组之间在正离子和负离子模式下53种和19种失调的代谢产物。苯乙烯降解和氨基糖-核苷酸糖代谢途径在正离子和负离子模式下分别有显著差异。此外，进一步进行了代谢组和微生物组之间的相关性分析，揭示了关键的微生物群和代谢产物。总之，我们成功地使用一定剂量的AOM/DSS建立了肿瘤模型，并鉴定了可能调节肿瘤发生的差异肠道微生物群和特征性代谢产物，从而为CRC的预防和治疗提供了新的概念。
