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炎症性肠病的种内差异:通过比较基因组学和代谢组学分析洞察潜在机制。

Intraspecific difference of in inflammatory bowel diseases: Insights into potential mechanisms through comparative genomics and metabolomics analyses.

作者信息

Liu Yaru, Duan Hui, Chen Ying, Zhang Chengcheng, Zhao Jianxin, Narbad Arjan, Tian Fengwei, Zhai Qixiao, Yu Leilei, Chen Wei

机构信息

State Key Laboratory of Food Science and Resources Jiangnan University Wuxi China.

School of Food Science and Technology Jiangnan University Wuxi China.

出版信息

Imeta. 2023 Sep 25;2(4):e136. doi: 10.1002/imt2.136. eCollection 2023 Nov.

DOI:10.1002/imt2.136
PMID:38868211
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10989848/
Abstract

Inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of the gastrointestinal tract that have become a global health burden. Studies have revealed that can effectively alleviate various immune diseases, including colitis, rheumatoid arthritis, and metabolic disorders. Here, we obtained 72 strains of from 120 fermentation and fecal samples across China. In total, 16 strains from different sources were initially screened in an in vitro Caco-2 model induced by dextran sulfate sodium. Subsequently, six strains (four exhibiting effectiveness and two exhibiting ineffectiveness) were selected for further validation in an in vivo colitis mouse model. The results demonstrated that strains exhibited varying degrees of amelioration of the colitis disease process. Notably, CCFM1267, the most effective strain, significantly restored colon length and tight-junction protein expression, and reduced the levels of cytokines and associated inflammatory enzymes. Moreover, CCFM1267 upregulated the abundance of , , and , leading to increased levels of acetic acid and propionic acid. Conversely, the other four strains ( QJSSZ1L4, QJSSZ4L10, QGZZYRHMT1L6, and QGZZYRHMT2L6) only exhibited a partial remission effect, while QJSNT1L10 displayed minimal impact. Therefore, CCFM1267 and QJSNT1L10 were selected for further exploration of the mechanisms underlying their differential mitigating effects. Comparative genomics analysis revealed significant variations between the two strains, particularly in genes associated with carbohydrate-active enzymes, such as the glycoside hydrolase family, which potentially contribute to the diverse profiles of short-chain fatty acids in vivo. Additionally, metabolome analysis demonstrated that acetylcholine and indole-3-acetic acid were the main differentiating metabolites of the two strains. Therefore, the strains of exhibited varying degrees of effectiveness in alleviating IBD-related symptoms, and the possible reasons for these variations were attributed to discrepancies in the carbohydrate-active enzymes and metabolites among the strains.

摘要

炎症性肠病(IBDs)是胃肠道的慢性炎症性疾病,已成为全球健康负担。研究表明,[具体物质未提及]可有效缓解包括结肠炎、类风湿性关节炎和代谢紊乱在内的各种免疫疾病。在此,我们从中国各地的120份发酵和粪便样本中获得了72株[具体物质未提及]。总共在硫酸葡聚糖钠诱导的体外Caco-2模型中初步筛选了来自不同来源的16株菌株。随后,选择了6株菌株(4株表现出有效性,2株表现出无效性)在体内结肠炎小鼠模型中进行进一步验证。结果表明,[具体物质未提及]菌株对结肠炎疾病进程表现出不同程度的改善。值得注意的是,最有效的菌株CCFM1267显著恢复了结肠长度和紧密连接蛋白表达,并降低了细胞因子和相关炎症酶的水平。此外,CCFM1267上调了[具体物质未提及]、[具体物质未提及]和[具体物质未提及]的丰度,导致乙酸和丙酸水平升高。相反,其他4株菌株(QJSSZ1L4、QJSSZ4L10、QGZZYRHMT1L6和QGZZYRHMT2L6)仅表现出部分缓解作用,而QJSNT1L10的影响最小。因此,选择CCFM1267和QJSNT1L10进一步探索其不同缓解作用的潜在机制。比较基因组学分析揭示了这两种菌株之间的显著差异,特别是在与碳水化合物活性酶相关的基因中,如糖苷水解酶家族,这可能导致体内短链脂肪酸的不同谱。此外,代谢组分析表明乙酰胆碱和吲哚-3-乙酸是这两种菌株的主要差异代谢物。因此,[具体物质未提及]菌株在缓解IBD相关症状方面表现出不同程度的有效性,这些差异的可能原因归因于菌株之间碳水化合物活性酶和代谢物的差异。

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