Introduction: Butyrate is a short-chain fatty acid metabolite produced by microbiota in the colon. With its antioxidant properties, butyrate has also been shown to alter the neurological functions in affective disorder models, suggesting it as a key mediator in gut-brain interactions. Objective: Here, we evaluated the negative effect of oxidative stress on the transport of the serotonin precursor tryptophan as present in affective disorders. Butyrate was hypothesized to be able to rescue these deficits due to its antioxidative capacities and its effect on transmembrane transport of tryptophan. Human skin-derived fibroblasts were used as cellular models to address these objectives. Methods: Human fibroblasts were treated with hydrogen peroxide to induce oxidative stress. Stressed as well as control cells were treated with different concentrations of butyrate. Tryptophan (³H) was used as a tracer to measure the transport of tryptophan across the cell membranes (n = 6). Furthermore, gene expression profiles of different amino acid transporters were analyzed (n = 2). Results: As hypothesized,oxidative stress significantly decreased the uptake of tryptophan in fibroblast cells, while butyrate counteracted this effect. Oxidative stress did not alter the gene expression profile of amino acid transporters. However, treatment of stressed and control cells with different concentrations of butyrate differentially regulated the gene expression of large amino acid transporters 1 and 2, which are the major transporters of tryptophan. Conclusions:Gut microbiota-derived butyrate may have therapeutic potential in affective disorders characterized by either aberrant serotonergic activity or neuroinflammation due to its role in rescuing the oxidative stress-induced perturbations of tryptophan transport.
Neuropsychobiology

中文翻译：

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丁酸盐可挽救氧化应激引起的色氨酸转运缺陷：对情感或肠脑轴障碍的潜在影响

简介：丁酸盐是一种短链脂肪酸代谢物，由结肠中的微生物群产生。由于其抗氧化特性，丁酸盐还被证明可以改变情感障碍模型中的神经功能，表明它是肠脑相互作用的关键介质。目的：在这里，我们评估了氧化应激对情感障碍中存在的血清素前体色氨酸转运的负面影响。由于丁酸盐的抗氧化能力及其对色氨酸跨膜转运的影响，假设丁酸盐能够挽救这些缺陷。人类皮肤来源的成纤维细胞被用作细胞模型来解决这些目标。方法：用过氧化氢处理人成纤维细胞以诱导氧化应激。用不同浓度的丁酸盐处理应激细胞和对照细胞。色氨酸 ( ³ H) 用作示踪剂以测量色氨酸跨细胞膜的转运 ( n = 6)。此外，分析了不同氨基酸转运蛋白的基因表达谱（n = 2）。结果：正如假设的那样，氧化应激显着降低了成纤维细胞对色氨酸的摄取，而丁酸盐则抵消了这种作用。氧化应激不会改变氨基酸转运蛋白的基因表达谱。然而，用不同浓度的丁酸盐处理应激细胞和对照细胞会差异调节大氨基酸转运蛋白 1 和 2 的基因表达，这些转运蛋白是色氨酸的主要转运蛋白。结论：肠道微生物群衍生的丁酸盐可能对以异常 5-羟色胺能活性或神经炎症为特征的情感障碍具有治疗潜力，因为其在挽救氧化应激诱导的色氨酸转运扰动中发挥作用。
神经心理生物学