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Abstract：
Inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of the gastrointestinal tract that have become a global health burden. Studies have revealed that Latilactobacillus sakei can effectively alleviate various immune diseases, including colitis, rheumatoid arthritis, and metabolic disorders. Here, we obtained 72 strains of L. sakei 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 L. sakei strains exhibited varying degrees of amelioration of the colitis disease process. Notably, L. sakei 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, L. sakei CCFM1267 upregulated the abundance of Enterorhabdus, Alloprevotella, and Roseburia, leading to increased levels of acetic acid and propionic acid. Conversely, the other four strains (L. sakei QJSSZ1L4, QJSSZ4L10, QGZZYRHMT1L6, and QGZZYRHMT2L6) only exhibited a partial remission effect, while L. sakei QJSNT1L10 displayed minimal impact. Therefore, L. sakei 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 L. sakei 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,沙木乳杆菌能有效缓解各种免疫性疾病,包括结肠炎,类风湿性关节炎,和代谢紊乱。这里,我们从全国120份发酵和粪便样品中获得了72株沙克L.总的来说,在葡聚糖硫酸钠诱导的体外Caco-2模型中初步筛选了16个来自不同来源的菌株。随后，选择6个菌株(4个显示有效,2个显示无效)在体内结肠炎小鼠模型中进行进一步验证.结果表明，沙鱼菌株对结肠炎的疾病过程有不同程度的改善。值得注意的是,L.sakeiCCFM1267，最有效的菌株，显著恢复结肠长度和紧密连接蛋白表达，并降低细胞因子和相关炎症酶的水平。此外，L.sakeiCCFM1267上调了肠道的丰度，Alloprevotella,和Roseburia,导致乙酸和丙酸含量增加。相反，其他四个菌株(L.SakeiQJSSZ1L4，QJSSZ4L10，QGZZYRHMT1L6和QGZZYRHMT2L6）仅表现出部分缓解效果，而L.sakeiQJSNT1L10显示最小的影响。因此,选择L.sakeiCCFM1267和QJSNT1L10用于进一步探索其不同缓解作用的潜在机制。比较基因组学分析显示两种菌株之间存在显着差异，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，这可能有助于体内短链脂肪酸的多样性。此外,代谢组分析表明，乙酰胆碱和吲哚-3-乙酸是两种菌株的主要差异代谢产物。因此,沙生L.sakei菌株在缓解IBD相关症状方面表现出不同程度的有效性，这些变化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。
