Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.
Free Radic Biol Med. 2021 Oct;174:110-120. doi: 10.1016/j.freeradbiomed.2021.08.002. Epub 2021 Aug 4.
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract whose occurrence is attributed to various factors, including genetic factors, immune response, microbial changes, and oxidative stress. Microbial-targeted therapy has emerged as an alternative to immunosuppressive therapy for IBD.
The effects of an atypical commensal Escherichia coli strain harboring an additional catalase gene (compared to typical E. coli strain) on dextran sulfate sodium (DSS)-induced colitis were explored in mice.
The atypical E. coli (atEc) significantly restored body weight, reduced disease activity score, and improved histological scores in mice with colitis. Hydrogen peroxide levels in colitis mice were noticeably decreased when the mice were administered atEc. The proinflammatory cytokine levels were decreased and regulatory T cell numbers were increased after the administration of atEc. The abundance of Firmicutes was significantly recovered, while that of Proteobacteria decreased in atEc -treated mice compared with that in vehicle-treated wild-type mice. To investigate the role of interleukin (IL)-17A in mediating the anti-inflammatory effects of the atEc, IL-17A‒knockout mice were orally administered atEc. Clinical and immune responses and microbial composition were significantly reduced in IL-17A‒knockout mice compared with those in wild-type mice.
atEc ameliorates colonic inflammation by controlling hydrogen peroxide levels, immune responses (including regulatory T cells and IL-17A), and microbial composition. atEc could be a novel candidate of probiotic for IBD treatment.
炎症性肠病（IBD）是一种胃肠道的慢性炎症性疾病，其发生归因于多种因素，包括遗传因素、免疫反应、微生物变化和氧化应激。微生物靶向治疗已成为 IBD 免疫抑制治疗的替代方法。
在患有葡聚糖硫酸钠（DSS）诱导结肠炎的小鼠中，研究了携带额外过氧化氢酶基因的非典型共生大肠杆菌菌株（与典型大肠杆菌菌株相比）对结肠炎的影响。
非典型大肠杆菌（atEc）可显著恢复结肠炎小鼠的体重、降低疾病活动评分并改善组织学评分。给予 atEc 后，结肠炎小鼠的过氧化氢水平明显降低。给予 atEc 后，促炎细胞因子水平降低，调节性 T 细胞数量增加。与给予载体的野生型小鼠相比，atEc 处理的小鼠厚壁菌门的丰度显著恢复，而变形菌门的丰度降低。为了研究白细胞介素（IL）-17A 在介导 atEc 的抗炎作用中的作用，口服给予 IL-17A 敲除小鼠 atEc。与野生型小鼠相比，IL-17A 敲除小鼠的临床和免疫反应以及微生物组成显著降低。
atEc 通过控制过氧化氢水平、免疫反应（包括调节性 T 细胞和 IL-17A）和微生物组成来改善结肠炎症。atEc 可能是治疗 IBD 的新型益生菌候选物。
