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Abstract：
BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.
OBJECTIVE: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development.
METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.
RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB\'s inhibition of CRC cell proliferation.
CONCLUSIONS: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.
OBJECTIVE: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development.
METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.
RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB\'s inhibition of CRC cell proliferation.
CONCLUSIONS: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.
摘要：
背景：结直肠癌（CRC）是全球最常见的恶性肿瘤之一。最近的报道表明，有核梭杆菌(F.核仁)有助于引发，programming,和CRC的预后。丁酸,一种来源于细菌发酵可溶性膳食纤维的短链脂肪酸,已知抑制各种癌症。本研究旨在探讨F.nucleatum是否通过影响肠代谢产物丁酸来影响CRC的发生和进展。
目的：探讨核菌影响CRC发生发展的机制。
方法:在口服F.核仁后观察到BALB/c小鼠的肠道微生物群的变化。此外,将DLD-1和HCT116细胞系在体外暴露于丁酸钠(NaB)和核仁F.以检查对增殖蛋白和线粒体功能的影响。
结果：我们的研究表明，来自CRC患者的粪便样本中的F.而产生丁酸的细菌的患病率明显较低。在有核F.的小鼠中，产生丁酸的细菌数量减少，导致丁酸水平改变，丁酸的关键肠道代谢产物。暴露于NaB会损害DLD-1和HCT116CRC细胞的线粒体形态并降低线粒体膜电位。因此,这导致三磷酸腺苷和活性氧的调制产生，从而抑制癌细胞增殖。此外,NaB触发一磷酸腺苷活化蛋白激酶（AMPK）信号通路，阻断HCT116和DLD-1细胞的细胞周期，抑制CRC细胞的增殖。F.核仁和NaB的组合存在减弱了后者的作用。通过使用小干扰RNA来抑制AMPK，证明AMPK对于NaB抑制CRC细胞增殖是必需的。
结论：F.核仁可以通过其对丁酸的抑制作用促进癌症进展，通过AMPK信号通路。
目的：探讨核菌影响CRC发生发展的机制。
方法:在口服F.核仁后观察到BALB/c小鼠的肠道微生物群的变化。此外,将DLD-1和HCT116细胞系在体外暴露于丁酸钠(NaB)和核仁F.以检查对增殖蛋白和线粒体功能的影响。
结果：我们的研究表明，来自CRC患者的粪便样本中的F.而产生丁酸的细菌的患病率明显较低。在有核F.的小鼠中，产生丁酸的细菌数量减少，导致丁酸水平改变，丁酸的关键肠道代谢产物。暴露于NaB会损害DLD-1和HCT116CRC细胞的线粒体形态并降低线粒体膜电位。因此,这导致三磷酸腺苷和活性氧的调制产生，从而抑制癌细胞增殖。此外,NaB触发一磷酸腺苷活化蛋白激酶（AMPK）信号通路，阻断HCT116和DLD-1细胞的细胞周期，抑制CRC细胞的增殖。F.核仁和NaB的组合存在减弱了后者的作用。通过使用小干扰RNA来抑制AMPK，证明AMPK对于NaB抑制CRC细胞增殖是必需的。
结论：F.核仁可以通过其对丁酸的抑制作用促进癌症进展，通过AMPK信号通路。
