Yang Chen, Huiting Fang, Haiqin Chen, Xiaoming Liu, Jianxin Zhao, Catherine Stanton, R Paul Ross, Wei Chen, Bo Yang
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引用次数: 0
摘要
结直肠癌(CRC)是全球第三大常见癌症。因此,迫切需要确定新的CRC预防和治疗策略。本研究旨在筛选对结直肠癌具有预防作用的有益菌,并阐明其潜在机制。首先,我们比较了健康志愿者和结直肠癌患者的肠道细菌和细菌代谢物,发现结直肠癌患者肠道共轭亚油酸(CLA)、丁酸和双歧杆菌明显低于健康志愿者,这些指标与结直肠癌呈显著负相关。接下来,建立自发性结直肠癌小鼠模型,探讨补充产cla双歧杆菌对结直肠癌的影响。小鼠补充产生cla的短双歧杆菌CCFM683和假atenulatum B. MY40C可显著预防结直肠癌。此外,分子方法表明CLA和产生CLA的基因bbi是CCFM683预防结直肠癌的关键代谢物和基因。抑制剂干预结果显示PPAR-γ是预防结直肠癌的关键受体。CCFM683抑制NF-κB信号通路,上调MUC2、Claudin-1、ZO-1,并通过CLA-PPAR-γ轴促进肿瘤细胞凋亡。此外,粪便微生物群移植(FMT)和宏基因组分析表明,CCFM683通过产生CLA上调内脏臭杆菌,进而通过产生丁酸、上调TJ蛋白、调节细胞因子和调节肠道微生物群来预防结直肠癌。这些结果将有助于双歧杆菌的临床试验和结直肠癌膳食产品的理论研究和开发。
Bifidobacterium inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation.
Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and Bifidobacterium in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing Bifidobacterium on CRC. Supplementation of mice with CLA-producing Bifidobacterium breve CCFM683 and B. pseudocatenulatum MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, bbi, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated Odoribacter splanchnicus through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of Bifidobacterium and the theoretical research and development of CRC dietary products.
期刊介绍:
The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more.
Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.