Lin Ting-Yun, Wu Wei-Kai, Hung Szu-Chun
Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Tzu Chi University, Hualien, Taiwan.
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, and Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
NPJ Biofilms Microbiomes. 2025 Jan 13;11(1):15. doi: 10.1038/s41522-025-00651-8.
Indoxyl sulfate (IS) has been implicated in the pathogenesis of cardiovascular diseases. IS is converted from indole, a metabolite of dietary tryptophan through the action of gut microbial tryptophanase, by two hepatic enzymes: CYP2E1 and SULT1A1. We hypothesized that the effect of tryptophan intake on IS production might differ from person to person. We enrolled 72 healthy persons (33 ± 7 years; 54.2% women) to undergo an oral tryptophan challenge test (OTCT), in which 7 blood samples were collected at 0, 4, 8, 12, 24, 36, and 48 h following oral administration of L-tryptophan 2000 mg. We observed high interindividual variability of IS production in the response to an OTCT. Twenty-four subjects in the lowest tertile of the baseline-adjusted area under the curve of IS were defined as low-IS producers, whereas 24 subjects in the highest tertile were defined as high-IS producers. There was no significant difference in baseline characteristics or CYP2E1 and SULT1A1-SNP genotyping distributions between the two IS-producing phenotypes. However, distinct differences in gut microbial composition were identified. In addition, the abundance of tryptophanase was significantly higher in the high-IS producers than in the low-IS producers (P = 0.01). The OTCT may serve as personalized dietary guidance. High-IS producers are more likely to be at greater risk of cardiovascular diseases and may benefit from consuming foods low in tryptophan. Potential clinical applications of the OTCT in precision nutrition warrant further investigation.
硫酸吲哚酚（IS）与心血管疾病的发病机制有关。IS由饮食中色氨酸的代谢产物吲哚经肠道微生物色氨酸酶作用，再通过两种肝脏酶：细胞色素P450 2E1（CYP2E1）和磺基转移酶1A1（SULT1A1）转化而来。我们推测色氨酸摄入对IS生成的影响可能因人而异。我们招募了72名健康人（33±7岁；54.2%为女性）进行口服色氨酸激发试验（OTCT），在口服2000 mg L-色氨酸后的0、4、8、12、24、36和48小时采集7份血样。我们观察到在OTCT反应中IS生成存在高度个体间变异性。将基线校正后IS曲线下面积最低三分位数的24名受试者定义为低IS生成者，而最高三分位数的24名受试者定义为高IS生成者。两种IS生成表型在基线特征或CYP2E1和SULT1A1-SNP基因分型分布上无显著差异。然而，肠道微生物组成存在明显差异。此外，高IS生成者中色氨酸酶的丰度显著高于低IS生成者（P = 0.01）。OTCT可作为个性化饮食指导。高IS生成者患心血管疾病的风险可能更高，食用色氨酸含量低的食物可能有益。OTCT在精准营养中的潜在临床应用值得进一步研究。
