Oral delivery of a Lactococcus lactis strain secreting bovine lactoferricin-lactoferrampin alleviates the development of acute colitis in mice
Oral delivery of a Lactococcus lactis strain secreting bovine lactoferricin-lactoferrampin alleviates the development of acute colitis in mice
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DOI：
10.1007/s00253-019-09898-6
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发表时间：
2019-08-01
影响因子：
5
通讯作者：
Tang, Lijie
中科院分区：
文献类型：
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作者：
Song, Liying;Xie, Weichun;Tang, Lijie
溃疡性结肠炎（UC）是一种慢性复发性疾病。UC的治疗将受益于治疗剂对肠的特异性靶向。以往的研究表明，牛乳铁蛋白和乳铁蛋白具有杀菌、抗炎和免疫调节作用。在这里，我们研究了口服牛乳铁蛋白-乳铁蛋白（LFCA）编码乳酸乳球菌（LL-LFCA）菌株是否可以减轻实验性结肠炎。LL-LFCA衍生的LFCA在体外抑制大肠杆菌和金黄色葡萄球菌的生长。在小鼠中，LL-LFCA给药降低了疾病活动指数，并减弱了葡聚糖硫酸钠（DSS）诱导的体重减轻和结肠缩短。LL-LFCA治疗还改善DSS诱导的结肠损伤，抑制炎性细胞浸润，显著降低髓过氧化物酶活性，并改善DSS诱导的肠通透性和紧密连接的破坏。此外，16 S rDNA测序显示LL-LFCA逆转DSS诱导的肠道生态失调。LL-LFCA给药也减少了血清和结肠中促炎介质的产生。在体外，LL-LFCA衍生的LFCA降低促炎因子的信使RNA表达。其潜在机制可能涉及抑制核因子-κ B（NF-κ B）通路。结果表明，LL-LFCA改善DSS诱导的小鼠肠损伤，提示LL-LFCA可能是治疗炎症性肠病的有效药物。
Ulcerative colitis (UC) is a chronic relapsing disease. Treatment of UC would benefit from specific targeting of therapeutics to the intestine. Previous studies have demonstrated that bovine lactoferricin and lactoferrampin have bactericidal, anti-inflammatory, and immunomodulatory effects. Here, we investigated whether oral administration of a bovine lactoferricin-lactoferrampin (LFCA)-encoding Lactococcus lactis (LL-LFCA) strain could alleviate experimental colitis. LFCA derived from LL-LFCA inhibited the growth of Escherichia coli and Staphylococcus aureus in vitro. In mice, administration of LL-LFCA decreased the disease activity index and attenuated dextran sulfate sodium (DSS)-induced body weight loss and colon shortening. LL-LFCA treatment also ameliorated DSS-induced colon damage, inhibited inflammatory cell infiltration, significantly decreased myeloperoxidase activity, and ameliorated DSS-induced disruption of intestinal permeability and tight junctions. In addition, 16S rDNA sequencing showed that LL-LFCA reversed DSS-induced gut dysbiosis. The production of proinflammatory mediators in serum and the colon was also reduced by administration of LL-LFCA. In vitro, LFCA derived from LL-LFCA decreased the messenger RNA expression of proinflammatory factors. The underlying mechanisms may involve inhibition of the nuclear factor kappa B (NF-kappa B) pathway. The results demonstrate that LL-LFCA ameliorates DSS-induced intestinal injury in mice, suggesting that LL-LFCA might be an effective drug for the treatment of inflammatory bowel diseases.