Among bacterial metabolites, hydrogen sulfide (H₂S) has received increasing attention. The epithelial cells of the large intestine are exposed to two sources of H₂S. The main one is the luminal source that results from specific bacteria metabolic activity towards sulfur-containing substrates. The other source in colonocytes is from the intracellular production mainly through cystathionine beta-synthase (CBS) activity. H₂S is oxidized by the mitochondrial sulfide oxidation unit, resulting in ATP synthesis, and thus establishing this compound as the first mineral energy substrate in colonocytes. However, when the intracellular H₂S concentration exceeds the colonocyte capacity for its oxidation, it inhibits the mitochondrial respiratory chain, thus affecting energy metabolism. Higher luminal H₂S concentration affects the integrity of the mucus layer and displays pro-inflammatory effects. However, a low/minimal amount of endogenous H₂S exerts an anti-inflammatory effect on the colon mucosa pointing out the ambivalent effect of H₂S depending on its intracellular concentration. Regarding colorectal carcinogenesis, forced CBS expression in late adenoma-like colonocytes increased their proliferative activity, bioenergetics capacity, and tumorigenicity; while genetic ablation of CBS in mice resulted in a reduced number of mutagen-induced aberrant crypt foci. Activation of endogenous H₂S production and low H₂S extracellular concentration enhance cancerous colorectal cells proliferation. Higher exogenous H₂S concentrations markedly reduce mitochondrial ATP synthesis and proliferative capacity in cancerous cells, enhance glycolysis, but do not affect their ATP cell content nor viability. Thus, it appears that, notably through an effect on colonocyte energy metabolism, endogenous and microbiota-derived H₂S are involved in the host intestinal physiology and physiopathology.

中文翻译：

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肠道菌群和上皮细胞产生硫化氢及其对结肠和直肠粘膜的影响

在细菌代谢物中，硫化氢（H ₂ S）受到越来越多的关注。大肠的上皮细胞暴露于两种H ₂ S来源。主要的一种是腔内来源，其源于特定细菌对含硫底物的代谢活性。结肠细胞中的其他来源主要是通过胱硫醚β-合酶（CBS）活性产生的细胞内产生。H ₂ S被线粒体硫化物氧化单元氧化，导致ATP合成，从而将该化合物确立为结肠细胞中的第一矿物能底物。但是，当细胞内H ₂S浓度超过结肠细胞的氧化能力，它抑制线粒体呼吸链，从而影响能量代谢。较高的腔内H ₂ S浓度会影响粘液层的完整性并显示促炎作用。然而，低/最小量的内源性H ₂ S对结肠粘膜产生抗炎作用，指出H ₂ S取决于其细胞内浓度的矛盾作用。关于结直肠癌的发生，在晚期腺瘤样结肠细胞中强迫CBS表达增加了它们的增殖活性，生物能能力和致瘤性。小鼠CBS的遗传消融导致诱变剂诱导的异常隐窝灶数量减少。激活内源性H₂ S产生和低H ₂ S细胞外浓度增强了癌性结直肠细胞的增殖。较高的外源H ₂ S浓度显着降低癌细胞中线粒体ATP的合成和增殖能力，增强糖酵解作用，但不影响其ATP细胞含量或生存能力。因此，似乎特别是通过对结肠细胞能量代谢的影响，内源性和微生物源性的H ₂ S参与宿主肠的生理和生理病理。