Xu Fuqiang, Li Qiaoqiao, Wang Shuyang, Dong Miaoyin, Xiao Guoqing, Bai Jin, Wang Junkai, Sun Xisi
Institute of Modern Physics, Chinese Academy of Sciences , Lanzhou, Gansu, China.
College of Nuclear Science and Technology, University of Chinese Academy of Sciences , Beijing, China.
Microbiol Spectr. 2023 Sep 1;11(5):e0018923. doi: 10.1128/spectrum.00189-23.
Gut microbiota and their secreted metabolites have an influence on the initiation and progression of colon cancer. Probiotics are extensively perceived as a potential microbiota-modulation strategy to promote the health of the host, while the effectiveness of preventing colon cancer based on microbiota therapy has not been confirmed, and antitumor mechanisms influenced by microbiota and their metabolites with the intervention of probiotics remain to be further investigated. , (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by in colon cancer models in mice. We demonstrated that the pre-administration of (JY300-8 and JMR-01) for 20 days before establishing tumor models resulted in an 86.21% reduction in tumor formation rate compared to tumor control group. Subsequently, continuous oral administration of living significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that suppresses colonic tumorigenesis and progression through the modulation of gut microbiota homeostasis and metabolites, including the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P), and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Additionally, metabolome analyses of (JY300-8 and JMR-01) indicate that living could reduce the relative abundance of alanine and L-serine to suppress tumor progression by regulating the tumor microenvironment, including down-regulation of pyrimidine metabolism and S1P signaling in cancer. These findings provide a potential prevention strategy and therapeutic target for colon cancer through the intervention of dietary . IMPORTANCE The modulation of gut microbiota and metabolites has a significant influence on the progression of colon cancer. Our research indicated that the intervention of probiotics is a potentially feasible strategy for preventing colon cancer. We have also revealed the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites, which could lead to broader biomedical impacts on the prevention and therapy of colon cancer with microbiota-based therapy regulated by probiotics.
肠道微生物群及其分泌的代谢产物对结肠癌的发生和发展有影响。益生菌被广泛认为是一种潜在的调节微生物群的策略,以促进宿主健康,然而基于微生物群疗法预防结肠癌的有效性尚未得到证实,并且在益生菌干预下微生物群及其代谢产物影响的抗肿瘤机制仍有待进一步研究。(JY300 - 8和JMR - 01)显著抑制了CT26、HT29和HCT116细胞的增殖。此外,我们通过改变小鼠结肠癌模型中肠道微生物群及其受调节的代谢产物,研究了及其潜在的抗肿瘤机制。我们证明,在建立肿瘤模型前20天预先施用(JY300 - 8和JMR - 01),与肿瘤对照组相比,肿瘤形成率降低了86.21%。随后,持续口服活的显著抑制肿瘤生长,肿瘤体积减少65.2%。微生物组和代谢组分析表明,通过调节肠道微生物群稳态和代谢产物,包括下调次级胆汁酸、鞘氨醇-1-磷酸(S1P)和嘧啶代谢,以及在荷瘤小鼠中产生抗癌化合物,抑制结肠肿瘤发生和进展。此外,(JY300 - 8和JMR - 01)的代谢组分析表明,活的可以通过调节肿瘤微环境,包括下调癌症中的嘧啶代谢和S1P信号传导,降低丙氨酸和L-丝氨酸的相对丰度来抑制肿瘤进展。这些发现为通过饮食干预提供了一种潜在预防结肠癌的策略和治疗靶点。重要性肠道微生物群和代谢产物的调节对结肠癌的进展有重大影响。我们的研究表明,益生菌干预是预防结肠癌的一种潜在可行策略。我们还通过改变肠道微生物群及其代谢产物揭示了潜在的抗肿瘤机制,这可能对基于益生菌调节微生物群的结肠癌预防和治疗产生更广泛的生物医学影响。