Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
J Gastrointest Cancer. 2020 Sep;51(3):738-747. doi: 10.1007/s12029-019-00329-3.
Colorectal cancer (CRC) is the third most common cancer in the world. Genetic backgrounds, lifestyle, and diet play an important role in CRC risk. The human gut microbiota has an influence on many features of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including CRC. It seems Warburg effect hypothesis corresponds to the early beginning of carcinogenesis because of eventual failure in the synthesis of a pyruvate dehydrogenase complex in cooperation with a supply of glucose in carbohydrates rich diets. From investigation among previous publications, we attempted to make it clear importance of Warburg effect in tumors; it also discusses the mechanisms of probiotics in inhibiting tumor progression and reverse Warburg effect of probiotics in modulating the microbiota and CRC therapies. These effects were observed in some clinical trials, the application of probiotics as a therapeutic agent against CRC still requirements further investigation.
Fiber is fermented by colonic bacteria into SCFAs such as butyrate/acetate, which may play a vital role in normal homeostasis by promoting turnover of the colonic epithelium. Butyrate enters the nucleus and functions as a histone deacetylase inhibitor (HDACi). Because cancerous colonocytes undertake the Warburg effect pathway, their favored energy source is glucose instead of butyrate. Therefore, accumulation of moderate concentrations of butyrate in cancerous colonocytes and role as HDACi. Probiotics have been shown to play a protective role against cancer development by modulating intestinal microbiota and immune response.
结直肠癌(CRC)是世界上第三大常见癌症。遗传背景、生活方式和饮食在 CRC 风险中起着重要作用。人类肠道微生物群对许多人体生理特征有影响,如代谢、营养吸收和免疫功能。微生物群的失衡与许多疾病有关,包括 CRC。似乎沃伯格效应假说与致癌作用的早期开始相对应,因为在富含碳水化合物的饮食中,丙酮酸脱氢酶复合物的合成与葡萄糖供应合作最终失败。从之前的出版物调查中,我们试图阐明沃伯格效应在肿瘤中的重要性;它还讨论了益生菌抑制肿瘤进展和逆转益生菌调节微生物群和 CRC 治疗的沃伯格效应的机制。这些效应在一些临床试验中得到了观察,益生菌作为治疗 CRC 的治疗剂的应用仍需要进一步研究。
纤维被结肠细菌发酵成 SCFAs,如丁酸盐/乙酸盐,通过促进结肠上皮的更新,可能在正常的体内平衡中发挥重要作用。丁酸盐进入细胞核,作为组蛋白去乙酰化酶抑制剂(HDACi)发挥作用。由于癌变的结肠细胞采用沃伯格效应途径,其首选能量来源是葡萄糖而不是丁酸盐。因此,中等浓度的丁酸盐在癌变结肠细胞中的积累和作为 HDACi 的作用。益生菌通过调节肠道微生物群和免疫反应,已被证明对癌症发展具有保护作用。