Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis.
Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis.
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多组学分析维生素 B6 代谢途径参与肝病发病机制
DOI：
10.2147/jhc.s370255
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发表时间：
2022
影响因子：
4.1
通讯作者：
Huang, Junqi
中科院分区：
文献类型：
--
作者：
Mei, Meihua;Liu, Danping;Tang, Xiuxin;You, Ying;Peng, Baogang;He, Xiaoshun;Huang, Junqi
目的分析肝硬化和失代偿期肝硬化患者血浆和组织中的微生物组学、代谢组学和蛋白质组学，探讨肝硬化发展为肝细胞癌（HCC）的调控机制。患者和方法收集44例HCC患者和28例DC患者的组织和血浆进行代谢组学分析。在9例HCC组织（HCCT）、4例远端非癌组织（HCCN）和11例DC组织（DCT）中进行16 S rRNA测序。5例HCC组织有肝硬化（HCCT-LC）。选取5例无肝硬化的肝癌组织（HCCT-NLC）和5例DCT组织进行蛋白质组测序。结合蛋白质组学和代谢组学分析，我们建立了一个小鼠慢性肝损伤模型，四氯化碳（CCl 4）和治疗他们与维生素B6（VB 6）。结果16 s rRNA序列分析结果显示，肝癌组织具有较高的α多样性。在HCCT中检测到最高LDA评分的是嗜酸金杆菌，在DCT中检测到亚斧杆菌，在HCCN中检测到寡养菌。代谢组学结果显示，癸酸、L-苏糖酸、胆碱、α-D-葡萄糖、D-核糖、甜菜碱、2 E-二十碳烯酸、亚油酸、L-棕榈酰肉毒碱、牛磺去氧胆酸、L-焦谷氨酸、硫酸雄酮和邻苯二甲酸单-2-乙基己酯（MEHP）等代谢产物的诊断效果优于AFP（AUC：0.852; 95% CI：0.749，0.954）。代谢组学和蛋白质组学联合分析发现，HCCT-LC组VB 6代谢紊乱、戊糖和葡萄糖醛酸互变比DCT组更明显，犬尿氨酸代谢紊乱在HCCT-LC组比HCCT-NLC组更明显。在CCl 4诱导的慢性肝损伤模型中，补充VB 6后，炎性细胞浸润、肝细胞水肿和变性显著改善。结论HCCT和DC的植物群分布存在明显差异，MEHP是HCC诊断的新标志物，VB 6可改善慢性肝损伤时炎性细胞浸润、肝细胞水肿和变性。
Purpose To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC). Patients and Methods Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6). Results 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved. Conclusion We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.