A Novel Postbiotic From Lactobacillus rhamnosus GG With a Beneficial Effect on Intestinal Barrier Function
A Novel Postbiotic From Lactobacillus rhamnosus GG With a Beneficial Effect on Intestinal Barrier Function
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来自鼠李糖乳杆菌 GG 的新型后生元对肠道屏障功能具有有益作用
DOI：
10.3389/fmicb.2019.00477
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发表时间：
2019-03-14
影响因子：
5.2
通讯作者：
Cao, Hong
中科院分区：
文献类型：
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作者：
Gao, Jie;Li, Yubin;Cao, Hong
人们早就知道益生菌可以用来维持肠道内稳态和治疗许多胃肠道疾病，但其潜在的机制仍然不清楚。近年来，越来越多的证据支持这样一种观点，即某些益生菌衍生成分，如细菌素、脂质胆酸、表面层蛋白和分泌蛋白，对肠道屏障功能具有与活菌相似的保护作用。这些生物活性成分在最近的出版物中被命名为“后生物”。我们之前发现鼠李糖乳杆菌GG （LGG）培养上清能够加速新生大鼠肠道防御成熟，防止新生大鼠口服大肠杆菌K1感染。然而，生物活性成分的身份尚未确定。在本研究中，我们使用液相色谱-串联质谱分析，鉴定了一种新的分泌蛋白（这里命名为HM0539）参与LGG培养上清的有益作用。对HM0539进行重组、纯化，并对其进行体内外生物活性的研究。我们的研究结果表明，HM0539对肠道屏障具有有效的保护作用，其表现为增强肠粘蛋白表达，防止脂多糖(LPS)-或肿瘤坏死因子α (TNF-α)-诱导的肠屏障损伤，包括下调肠粘蛋白（MUC2）、闭塞带-1 （ZO-1）和破坏肠道完整性。通过口服途径感染大肠杆菌K1的新生大鼠模型，我们验证了HM0539足以促进新生儿肠道防御的发展，并预防大肠杆菌K1的发病机制。此外，我们进一步扩展了HM0539的作用，发现它具有预防葡聚糖硫酸钠（DSS）诱导的结肠炎以及LPS/ d -半乳糖胺诱导的细菌易位和肝损伤的潜力。综上所述，我们鉴定出一种对肠道屏障功能具有保护作用的新型LGG后生物HM0539。我们的研究结果表明，HM0539有潜力成为预防和治疗肠屏障功能障碍相关疾病的有用药物。
It has long been known that probiotics can be used to maintain intestinal homeostasis and treat a number of gastrointestinal disorders, but the underlying mechanism has remained obscure. Recently, increasing evidence supports the notion that certain probiotic-derived components, such as bacteriocins, lipoteichoic acids, surface layer protein and secreted protein, have a similar protective role on intestinal barrier function as that of live probiotics. These bioactive components have been named ‘postbiotics’ in the most recent publications. We previously found that the Lactobacillus rhamnosus GG (LGG) culture supernatant is able to accelerate the maturation of neonatal intestinal defense and prevent neonatal rats from oral Escherichia coli K1 infection. However, the identity of the bioactive constituents has not yet been determined. In this study, using liquid chromatography-tandem mass spectrometry analysis, we identified a novel secreted protein (named HM0539 here) involved in the beneficial effect of LGG culture supernatant. HM0539 was recombinated, purified, and applied for exploring its potential bioactivity in vitro and in vivo. Our results showed that HM0539 exhibits a potent protective effect on the intestinal barrier, as reflected by enhancing intestinal mucin expression and preventing against lipopolysaccharide (LPS)- or tumor necrosis factor α (TNF-α)-induced intestinal barrier injury, including downregulation of intestinal mucin (MUC2), zonula occludens-1 (ZO-1) and disruption of the intestinal integrity. Using a neonatal rat model of E. coli K1 infection via the oral route, we verified that HM0539 is sufficient to promote development of neonatal intestinal defense and prevent against E. coli K1 pathogenesis. Moreover, we further extended the role of HM0539 and found it has potential to prevent dextran sulfate sodium (DSS)-induced colitis as well as LPS/D-galactosamine-induced bacterial translocation and liver injury. In conclusion, we identified a novel LGG postbiotic HM0539 which exerts a protective effect on intestinal barrier function. Our findings indicated that HM0539 has potential to become a useful agent for prevention and treatment of intestinal barrier dysfunction- related diseases.