微生物和代谢组学揭示了肥胖相关结直肠癌中互利共生的微生物-微生物相互作用。

Microbial and metabolic profiles unveil mutualistic microbe-microbe interaction in obesity-related colorectal cancer.

机构信息

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong Province, China.

出版信息

Cell Rep Med. 2024 Mar 19;5(3):101429. doi: 10.1016/j.xcrm.2024.101429. Epub 2024 Feb 19.

Abstract

Obesity is a risk factor for colorectal cancer (CRC), and the involvement of gut microbiota in the pathogenesis of obesity and CRC is widely recognized. However, the landscape of fecal microbiome and metabolome distinguishing patients with obesity-related CRC from obesity remains unknown. Here, we utilize metagenomic sequencing and metabolomics from 522 patients with CRC and healthy controls to identify the characteristics of obese CRC. Our integrated analysis reveals that obesity-related CRC is characterized by elevated Peptostreptococcus stomatis, dysregulated fatty acids and phospholipids, and altered Kyoto Encyclopedia of Genes and Genomes pathways involving glycerophospholipid metabolism and lipopolysaccharide synthesis. Correlation analysis unveils microbial interactions in obesity, where the probiotic Faecalibacterium prausnitzii and the tumor-promoting species P. stomatis may engage in cross-feeding, thereby promoting tumorigenesis. In vitro experiments affirm enhanced growth under cross-feeding conditions. The mutualistic microbe-microbe interaction may contribute to the association between obesity and elevated CRC risk. Additionally, diagnostic models incorporating BMI-specific microbial biomarkers display promise for precise CRC screening.

摘要

肥胖是结直肠癌(CRC)的一个风险因素,肠道微生物群在肥胖和 CRC 的发病机制中的作用已得到广泛认可。然而,区分肥胖相关 CRC 患者与肥胖症患者的粪便微生物群和代谢组学图谱尚不清楚。在这里,我们利用来自 522 名 CRC 患者和健康对照者的宏基因组测序和代谢组学数据来识别肥胖相关 CRC 的特征。我们的综合分析表明,肥胖相关 CRC 的特征是口腔普雷沃氏菌(Peptostreptococcus stomatis)升高、脂肪酸和磷脂失调以及涉及甘油磷脂代谢和脂多糖合成的京都基因与基因组百科全书途径改变。相关性分析揭示了肥胖症中的微生物相互作用,其中益生菌粪真杆菌(Faecalibacterium prausnitzii)和促肿瘤物种口腔普雷沃氏菌(P. stomatis)可能存在交叉喂养,从而促进肿瘤发生。体外实验证实了在交叉喂养条件下的增强生长。这种互惠的微生物-微生物相互作用可能是肥胖与 CRC 风险升高之间关联的原因之一。此外,包含 BMI 特异性微生物生物标志物的诊断模型显示出用于精确 CRC 筛查的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7cc1/10982962/e9662c4310d2/fx1.jpg

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