肠道菌群及其分泌的代谢物对结肠癌的发生和发展有影响。益生菌被广泛看作是一种潜在的菌群调节策略，用以促进宿主健康，但其在预防结肠癌方面的有效性尚未得到证实，且在益生菌干预下微生物群落和其代谢物所影响的抗肿瘤机制仍需进一步研究。体外实验中，乳酸菌（JY300-8和JMR-01）显著抑制了CT26，HT29和HCT116细胞的增殖。此外，我们通过乳酸菌在小鼠结肠癌模型中改变肠道菌群及其代谢物的作用研究了乳酸菌的预防和治疗效果及其潜在抗肿瘤机制。我们证明在建立肿瘤模型前的20天预先给予乳酸菌（JY300-8和JMR-01）可使肿瘤形成率减少86.21％，相较于肿瘤对照组。随后，持续口服乳酸菌显著抑制肿瘤生长，肿瘤体积减小了65.2％。微生物组和代谢组分析显示，乳酸菌通过调节肠道菌群稳态和代谢物，包括下调次级胆汁酸、鞘氨醇磷酸（S1P）和嘧啶代谢，以及产生抗癌化合物来抑制结肠肿瘤发生和发展。此外，乳酸菌（JY300-8和JMR-01）的代谢组分析表明，存活的乳酸菌通过调节肿瘤微环境，包括下调嘧啶代谢和S1P信号通路，来减少丙氨酸和L丝氨酸的相对丰度以抑制肿瘤发展。这些发现为通过饮食中的乳酸菌干预提供了潜在的结肠癌预防策略和治疗靶点。意义重大。肠道菌群和代谢物的调节对结肠癌的发展具有重要影响。我们的研究表明益生菌的干预是一种潜在可行的预防结肠癌的策略。我们还揭示了通过改变肠道菌群及其代谢物的作用的潜在抗肿瘤机制，这可能对通过益生菌调控的微生物组治疗在结肠癌预防和治疗方面产生更广泛的生物医学影响。

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. In vitro, Lactobacillus (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of Lactobacillus and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by Lactobacillus in colon cancer models in mice. We demonstrated that the pre-administration of Lactobacillus (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 Lactobacillus significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that Lactobacillus 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 Lactobacillus (JY300-8 and JMR-01) indicate that living Lactobacillus 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 Lactobacillus. 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.