Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis,Cell Host & Microbe

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Engineered probiotic ameliorates ulcerative colitis by restoring gut microbiota and redox homeostasis
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-08-27 , DOI: 10.1016/j.chom.2024.07.028
Peilin Guo ₁ , Wenjing Wang ₂ , Qian Xiang ₃ , Chao Pan ₄ , Yefeng Qiu ₅ , Tingting Li ₆ , Dongfang Wang ₇ , Jian Ouyang ₆ , Rongrong Jia ₈ , Min Shi ₈ , Yugang Wang ₈ , Junxia Li ₉ , Jiale Zou ₁₀ , Yuan Zhong ₁₁ , Jiawei Zhao ₂ , Diwei Zheng ₂ , Yimin Cui ₃ , Guanghui Ma ₁ , Wei Wei ₁

Affiliation

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing 100190, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P.R. China; Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing 100190, P.R. China.
Institute of Clinical Pharmacology, Peking University First Hospital, Beijing 100191, P.R. China.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing 100071, P.R. China.
Laboratory Animal Center of the Academy of Military Medical Sciences, Beijing 100071, P.R. China.
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China.
Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, P.R. China.
Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.
Department of Gastroenterology, Peking University First Hospital, Beijing 100034, P.R. China.
Department of Gastroenterology, The Second Medical Centre, Chinese PLA General Hospital, Beijing 100853, P.R. China.
State Key Laboratory of Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130015, P.R. China.

Probiotics are potential treatments for ulcerative colitis (UC), but their efficacy is frequently compromised by gastrointestinal conditions that limit adhesion and activity. Here, we use machine learning and bioinformatics to confirm that patients with UC have decreased prevalence of Lactobacillus genus and increased oxidative stress, which correlate with inflammation severity. Accordingly, we developed a probiotic-based therapeutic that synergistically restores intestinal redox and microbiota homeostasis. Lactobacillus casei (Lac) were induced to form a pericellular film, providing a polysaccharide network for spatially confined crystallization of ultrasmall but highly active selenium dots (Se-Lac). Upon oral administration, the selenium dot-embedded pericellular film efficiently enhanced gastric acid resistance and intestinal mucoadhesion of Lac cells. At the lesion site, the selenium dots scavenged reactive oxygen species, while Lac modulated the gut microbiota. In multiple mouse models and non-human primates, this therapeutic effectively relieved inflammation and reduced colonic damage, thus showing promise as a UC treatment.

中文翻译：

工程益生菌通过恢复肠道微生物群和氧化还原稳态来改善溃疡性结肠炎

益生菌是溃疡性结肠炎（UC）的潜在治疗方法，但它们的疗效经常受到限制粘附和活性的胃肠道疾病的影响。在这里，我们使用机器学习和生物信息学来确认 UC 患者的乳酸杆菌属患病率降低，氧化应激增加，这与炎症的严重程度相关。因此，我们开发了一种基于益生菌的疗法，可协同恢复肠道氧化还原和微生物群稳态。干酪乳杆菌（Lac）被诱导形成细胞周围膜，为超小但高活性硒点（Se-Lac）的空间限制结晶提供多糖网络。口服给药后，硒点嵌入的细胞周膜有效地增强了 Lac 细胞的胃酸抵抗力和肠粘膜粘附性。在病变部位，硒点清除活性氧，而 Lac 调节肠道微生物群。在多种小鼠模型和非人灵长类动物中，这种疗法有效缓解了炎症并减少了结肠损伤，因此显示出作为 UC 治疗的前景。

更新日期：2024-08-27

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