Xue Shenglong, Shi Tian, Xie Jinjin, Liu Weidong, Yao Shanxia, Li Na, Liu Huan, Kong Wenjie, Gao Feng
College of Life Science and Technology, Xinjiang University, Urumqi, China.
Department of Gastroenterology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China.
J Transl Med. 2025 Sep 1;23(1):972. doi: 10.1186/s12967-025-06991-5.
Genes and gluten intake are necessary but not sufficient to cause celiac disease (CeD), and altered intestinal flora is an additional risk factor for the development of CeD. The present study was conducted to investigate the intestinal flora and metabolic characteristics of CeD among the Chinese population, with the use of CeD patients from Xinjiang, China.
Macrogenomic sequencing was performed to analyze the composition and differences of the intestinal flora of 40 CeD patients and 40 healthy subjects. Non-targeted metabolomics analysis was carried out using LC-MS metabolomics technology in 30 CeD patients and 30 control subjects. A model for CeD diagnosis was constructed based on differential flora and metabolites. Blood was collected from all subjects for HLA typing assay.
CeD-associated alterations were identified in the gut microbiome and metabolome. 15 differential bacterial strains (AUC = 0.85) and 8 differential metabolites (AUC = 0.9799) constructed a diagnostic panel that was effective in differentiating CeD patients from healthy subjects. Compared with non-CeD patients carrying HLA-DQ, the abundances of Agathobacter_rectalis, Bifidobacterium_pseudocatenulatum, Clostridia_bacterium, Coprococcus_comes, and Fusicatenibacter_saccharivorans in CeD patients were significantly lower (P < 0.05). Metabolomics analysis showed that Leoheteronin D, Pc (34:2), and GPEtn (18:1/16:0) were the major metabolites involved in multiple metabolic pathways in CeD patients.
Our study revealed specific alterations in the gut microbiome and metabolome of Chinese CeD patients through a multi-omics integration strategy. We found that CeD individuals carrying CeD risk genes may possess a unique intestinal flora composition, and this intestinal flora may, to some extent, explain the pathogenesis of CeD beyond the contributions of genes and gluten intake.
基因和麸质摄入是引发乳糜泻（CeD）的必要条件，但并非充分条件，而肠道菌群改变是CeD发生发展的另一个风险因素。本研究旨在利用来自中国新疆的CeD患者，调查中国人群中CeD患者的肠道菌群及代谢特征。
对40例CeD患者和40例健康受试者进行宏基因组测序，分析肠道菌群的组成及差异。对30例CeD患者和30例对照受试者采用液相色谱-质谱代谢组学技术进行非靶向代谢组学分析。基于差异菌群和代谢产物构建CeD诊断模型。采集所有受试者的血液进行HLA分型检测。
在肠道微生物组和代谢组中发现了与CeD相关的改变。15种差异菌株（AUC = 0.85）和8种差异代谢产物（AUC = 0.9799）构建了一个诊断面板，可有效区分CeD患者和健康受试者。与携带HLA-DQ的非CeD患者相比，CeD患者中直肠阿加菌、假链状双歧杆菌、梭菌属细菌、共生粪球菌和食糖融合杆菌的丰度显著降低（P < 0.05）。代谢组学分析表明，Leoheteronin D、Pc（34:2）和GPEtn（18:1/16:0）是CeD患者多种代谢途径中的主要代谢产物。
我们的研究通过多组学整合策略揭示了中国CeD患者肠道微生物组和代谢组的特定改变。我们发现携带CeD风险基因的CeD个体可能具有独特的肠道菌群组成，并且这种肠道菌群在一定程度上可能解释了CeD的发病机制，而不仅仅是基因和麸质摄入的作用。
