The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, China.
Front Immunol. 2022 Sep 7;13:937539. doi: 10.3389/fimmu.2022.937539. eCollection 2022.
Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography-mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.
代谢状态和肠道微生物群与银屑病有关。甲氨蝶呤（MTX）通常是治疗这种疾病的一线药物。然而，MTX 与宿主代谢状态和肠道微生物群之间的关系尚不清楚。本研究旨在描述接受 MTX 治疗后银屑病患者的血液代谢组和肠道微生物组的特征。从 15 名银屑病患者中采集血清和粪便样本。分别应用非靶向液相色谱-质谱和宏基因组测序来描绘血液代谢组和肠道微生物组。我们发现，基线时代谢组学和宏基因组学特征决定了对 MTX 的反应，例如，血清营养分子水平高和肠道微生物群丰富的患者反应较差。经过 16 周的 MTX 治疗，我们观察到微生物活性途径减少，反应良好的患者表现出更多的微生物活性和较少的血清脂肪酸合成。我们还发现 MTX 干预前血清代谢组与肠道微生物组之间存在关联。微生物内的碳水化合物代谢、转运系统和蛋白质合成与宿主脂质、苯并类和有机酸的代谢簇有关。这些发现表明，血液和肠道微生物群的代谢状态参与了 MTX 在银屑病中的疗效，抑制共生肠道微生物群可能是 MTX 的作用机制之一。需要更大样本量的前瞻性研究来证实这些发现。
