Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, Hubei University of Technology, Wuhan, 430068, China.
Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul, 08826, South Korea.
Microb Cell Fact. 2022 Jun 7;21(1):113. doi: 10.1186/s12934-022-01840-2.
Inflammatory bowel disease (IBD) is a gastrointestinal disease characterized by diarrhea, rectal bleeding, abdominal pain, and weight loss. Recombinant probiotics producing specific proteins with IBD therapeutic potential are currently considered novel drug substitutes. In this study, a Bifidobacterium bifidum BGN4-SK strain was designed to produce the antioxidant enzymes streptococcal superoxide dismutase (SOD) and lactobacillus catalase (CAT), and a B. bifidum BGN4-pBESIL10 strain was proposed to generate an anti-inflammatory cytokine, human interleukin (IL)-10. In vitro and in vivo efficacy of these genetically modified Bifidobacterium strains were evaluated for colitis amelioration.
In a lipopolysaccharide (LPS)-stimulated HT-29 cell model, tumor necrosis factor (TNF)-α and IL-8 production was significantly suppressed in the B. bifidum BGN4-SK treatment, followed by B. bifidum BGN4-pBESIL10 treatment, when compared to the LPS-treated control. Synergistic effects on TNF-α suppression were also observed. In a dextran sodium sulphate (DSS)-induced colitis mouse model, B. bifidum BGN4-SK treatment significantly enhanced levels of antioxidant enzymes SOD, glutathione peroxidase (GSH-Px) and CAT, compared to the DSS-only group. B. bifidum BGN4-SK significantly ameliorated the symptoms of DSS-induced colitis, increased the expression of tight junction genes (claudin and ZO-1), and decreased pro-inflammatory cytokines IL-6, IL-1β and TNF-α.
These findings suggest that B. bifidum BGN4-SK ameliorated DSS-induced colitis by generating antioxidant enzymes, maintaining the epithelial barrier, and decreasing the production of pro-inflammatory cytokines. Although B. bifidum BGN4-pBESIL10 exerted anti-inflammatory effects in vitro, the enhancement of IL-10 production and alleviation of colitis were very limited.
炎症性肠病（IBD）是一种以腹泻、直肠出血、腹痛和体重减轻为特征的胃肠道疾病。目前，具有 IBD 治疗潜力的特定蛋白质的重组益生菌被认为是新型药物替代品。在这项研究中，设计了一株双歧杆菌 BGN4-SK 产生抗氧化酶链格孢菌超氧化物歧化酶（SOD）和乳杆菌过氧化氢酶（CAT），并提出了一株双歧杆菌 BGN4-pBESIL10 产生抗炎细胞因子人白细胞介素（IL）-10。评估了这些基因修饰双歧杆菌菌株在改善结肠炎方面的体外和体内疗效。
在脂多糖（LPS）刺激的 HT-29 细胞模型中，与 LPS 处理的对照组相比，双歧杆菌 BGN4-SK 处理显著抑制肿瘤坏死因子（TNF）-α和 IL-8 的产生，随后是双歧杆菌 BGN4-pBESIL10 处理。还观察到对 TNF-α抑制的协同作用。在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中，与 DSS 组相比，双歧杆菌 BGN4-SK 处理显著提高了抗氧化酶 SOD、谷胱甘肽过氧化物酶（GSH-Px）和 CAT 的水平。双歧杆菌 BGN4-SK 显著改善了 DSS 诱导的结肠炎症状，增加了紧密连接基因（claudin 和 ZO-1）的表达，并降低了促炎细胞因子 IL-6、IL-1β和 TNF-α的水平。
这些发现表明，双歧杆菌 BGN4-SK 通过产生抗氧化酶、维持上皮屏障和减少促炎细胞因子的产生来改善 DSS 诱导的结肠炎。虽然双歧杆菌 BGN4-pBESIL10 在体外表现出抗炎作用，但增强 IL-10 产生和缓解结肠炎的作用非常有限。
