Blachier François, Beaumont Martin, Andriamihaja Mireille, Davila Anne-Marie, Lan Annaïg, Grauso Marta, Armand Lucie, Benamouzig Robert, Tomé Daniel
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
UMR Physiologie de la Nutrition et du Comportement Alimentaire, AgroParisTech, INRA, Université Paris-Saclay, Paris, France.
Am J Pathol. 2017 Mar;187(3):476-486. doi: 10.1016/j.ajpath.2016.11.015. Epub 2017 Jan 9.
Evidence, mostly from experimental models, has accumulated, indicating that modifications of bacterial metabolite concentrations in the large intestine luminal content, notably after changes in the dietary composition, may have important beneficial or deleterious consequences for the colonic epithelial cell metabolism and physiology in terms of mitochondrial energy metabolism, reactive oxygen species production, gene expression, DNA integrity, proliferation, and viability. Recent data suggest that for some bacterial metabolites, like hydrogen sulfide and butyrate, the extent of their oxidation in colonocytes affects their capacity to modulate gene expression in these cells. Modifications of the luminal bacterial metabolite concentrations may, in addition, affect the colonic pH and osmolarity, which are known to affect colonocyte biology per se. Although the colonic epithelium appears able to face, up to some extent, changes in its luminal environment, notably by developing a metabolic adaptive response, some of these modifications may likely affect the homeostatic process of colonic epithelium renewal and the epithelial barrier function. The contribution of major changes in the colonocyte luminal environment in pathological processes, like mucosal inflammation, preneoplasia, and neoplasia, although suggested by several studies, remains to be precisely evaluated, particularly in a long-term perspective.
大多来自实验模型的证据不断积累,表明大肠管腔内容物中细菌代谢物浓度的改变,尤其是在饮食组成变化之后,就线粒体能量代谢、活性氧生成、基因表达、DNA完整性、增殖和活力而言,可能对结肠上皮细胞的代谢和生理产生重要的有益或有害影响。最近的数据表明,对于一些细菌代谢物,如硫化氢和丁酸盐,它们在结肠细胞中的氧化程度会影响其调节这些细胞中基因表达的能力。此外,管腔细菌代谢物浓度的改变可能会影响结肠的pH值和渗透压,而众所周知,这本身就会影响结肠细胞生物学。尽管结肠上皮在一定程度上似乎能够应对其管腔环境的变化,特别是通过产生代谢适应性反应,但其中一些改变可能会影响结肠上皮更新的稳态过程和上皮屏障功能。结肠细胞管腔环境的重大变化在诸如黏膜炎症、癌前病变和肿瘤形成等病理过程中的作用,尽管有几项研究提出了相关暗示,但仍有待精确评估,尤其是从长期角度来看。