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鼠李糖乳杆菌 KBL697 与肿瘤坏死因子-α 抑制剂英夫利昔单抗联合应用可改善结肠炎。

Co-administration of Lactobacillus gasseri KBL697 and tumor necrosis factor-alpha inhibitor infliximab improves colitis in mice.

机构信息

Department of Environmental Health Sciences, Graduate School of Public Health, Seoul National University, Seoul, Republic of Korea.

Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea.

出版信息

Sci Rep. 2022 Jun 10;12(1):9640. doi: 10.1038/s41598-022-13753-6.

Abstract

Inflammatory bowel disease (IBD) refers to disorders involving chronic inflammation of the gastrointestinal tract. Well-established treatments for IBD have not yet to be suggested. To address this gap, we investigated the effects of co-administration of Lactobacillus gasseri (L. gasseri) KBL697 and infliximab (IFX), the first approved tumor necrosis factor (TNF)-alpha inhibitor, on the dextran sodium sulfate-induced colitis mouse model. 2 × 10 colony-forming units/g of L. gasseri KBL697 were administered to seven-week-old female C57BL/6J mice daily by oral gavage. On day three, IFX (5 mg/kg) suspended in 1 × PBS (200 µL) was intravenously injected in the IFX-treated group and all mice were sacrificed on day nine. Co-administration of L. gasseri KBL697 and IFX improved colitis symptoms in mice, including body weight, disease activity index, colon length, and histology score. Additionally, pro-inflammatory cytokines, such as interferon-gamma, interleukin (IL)-2, IL-6, IL-17A, and TNF were significantly decreased, while IL-10, an anti-inflammatory cytokine, was increased. Expression levels of tight junction genes and CD4 + CD25 + Foxp3 + T regulatory cells in the mesenteric lymph nodes were synergistically upregulated with the combined treatment. Furthermore, co-administered mice displayed altered cecum microbial diversity and composition with increases in the genus Prevotella. Related changes in the predicted amino and nucleic acid metabolic pathways were also evident, along with increased acetate and butyrate level. Therefore, the synergistic effect of L. gasseri KBL697 and IFX co-administration is a possible method of prevention and treatment for IBD.

摘要

炎症性肠病(IBD)是指涉及胃肠道慢性炎症的疾病。目前尚未提出针对 IBD 的既定治疗方法。为了解决这一差距,我们研究了联合使用干酪乳杆菌 KBL697 和英夫利昔单抗(IFX)对葡聚糖硫酸钠诱导的结肠炎小鼠模型的影响。IFX 组在第 3 天通过尾静脉注射 5mg/kg 的 IFX 溶于 1×PBS(200µL),在第 9 天处死所有小鼠。每日通过口服灌胃给予 7 周龄雌性 C57BL/6J 小鼠 2×10 个菌落形成单位/g 的干酪乳杆菌 KBL697。干酪乳杆菌 KBL697 和 IFX 的联合使用改善了结肠炎小鼠的症状,包括体重、疾病活动指数、结肠长度和组织学评分。此外,促炎细胞因子如干扰素-γ、白细胞介素(IL)-2、IL-6、IL-17A 和 TNF 显著减少,而抗炎细胞因子 IL-10 增加。联合治疗还协同上调肠系膜淋巴结中紧密连接基因和 CD4+CD25+Foxp3+T 调节细胞的表达水平。此外,联合给药的小鼠盲肠微生物多样性和组成发生改变,普雷沃氏菌属增加。预测的氨基酸和核酸代谢途径也出现了相关变化,同时乙酸盐和丁酸盐水平增加。因此,干酪乳杆菌 KBL697 和 IFX 联合使用的协同作用可能是预防和治疗 IBD 的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3749/9187735/91007699a4e0/41598_2022_13753_Fig1_HTML.jpg

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