肠道微生物代谢驱动MSH2缺乏的结肠上皮细胞的转化
Antoaneta Belcheva1, Thergiory Irrazabal1, Susan J Robertson1
1Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cell
|July 19, 2014
概括
改变肠道微生物群或减少碳水化合物可以对抗小鼠的结直肠癌 (CRC). 肠道微生物通过用碳水化合物代谢产物来推动结肠细胞生长来促进CRC,而不是炎症或变异原体.
科学领域:
- 胃肠病学和肝病学
- 在瘤学瘤学.
- 微生物学 微生物学
背景情况:
- 结肠直肠癌 (CRC) 的病因涉及不匹配修复 (MMR) 和腺多样性大肠杆菌 (APC) 蛋白质缺乏,饮食,炎症和肠道微生物群.
- 微生物群和其他CRC病因因子之间的协同机制尚不清楚.
研究的目的:
- 阐明肠道微生物群与MMR缺乏和饮食相互作用以促进CRC的机制.
- 研究碳水化合物衍生代谢物在特定小鼠模型中的CRC发育中的作用.
主要方法:
- 使用APC(Min/+) MSH2(-/-) 鼠标来模拟CRC的发展.
- 操纵肠道微生物群的组成和食碳水化合物含量.
- 评估了CRC发生率,炎症反应,DNA突变原体的产生和结肠上皮细胞的增殖.
主要成果:
- 改变肠道微生物群组成或减少饮食中的碳水化合物显著降低了APC中的CRC.
- 肠道微生物通过提供碳水化合物衍生代谢物,如酸盐来促进CRC,这些代谢物促进MSH2的过度增殖-/-) 结肠上皮细胞.
- MMR途径影响β-catenin活性和结肠中通过增强细胞分化.
结论:
- 肠道微生物群,特别是通过碳水化合物代谢,在MMR缺乏的情况下,在CRC诱导中发挥着关键作用.
- 针对碳水化合物摄入的饮食干预可以减轻与特定微生物和遗传因素相关的CRC风险.
- 这种MMR途径参与调节与结肠癌发展相关的关键细胞过程.
相关概念视频
01:20Mismatch Repair
5.4K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.4K
01:36Mismatch Repair
37.9K
Overview
37.9K
01:18Functions of the Gut Microbiota
145
The gut microbiota includes trillions of microorganisms that colonize the human gastrointestinal tract, including bacteria, archaea, viruses, and fungi. This complex ecosystem plays a critical role in maintaining intestinal and systemic health. Most of these microbes inhabit the large intestine, establishing a relatively stable and diverse community that contributes to gut homeostasis through various metabolic, immunological, and protective mechanisms.Dominant bacterial phyla, such as...
145
01:27Microbiota of the Large Intestine
94
The large intestine hosts the most densely populated microbial ecosystem in the human body. This complex community primarily consists of anaerobic bacteria, with Bacillota (formerly Firmicutes) and Bacteroidota (formerly Bacteroidetes) as the predominant groups. The distribution of these microbes varies along different sections of the large intestine, influenced by local environmental factors such as oxygen availability and nutrient composition.The cecum, located at the beginning of the large...
94
01:26Transformation
1.3K
Microbial communities are dynamic environments where cell lysis releases free DNA into the surroundings. Other cells can take up this extracellular DNA through a process known as transformation.When a cell incorporates this foreign DNA into its genome, resulting in genetic modification, the process is known as transformation. Cells capable of this process are termed competent. Competence can be natural, as observed in certain bacteria and archaea, or artificially induced in the...
1.3K
01:27Microbiota of the Stomach and Small Intestine
74
The human gastrointestinal (GI) tract is characterized by distinct physicochemical conditions that shape its microbial communities. Among these, the stomach presents a particularly challenging environment for microbial colonization due to its highly acidic pH, ranging from 1 to 3. This extreme acidity effectively limits microbial density. However, certain acid-tolerant microorganisms are capable of surviving in this niche. Notably, Helicobacter pylori can colonize the gastric mucosa,...
74