Yang Jiali, Tan Shaochong, Ge Shengchan, Yang Mingzhu, Liu Hua, Liu Wei, Zhang Kaixiang, Zhang Zhenzhong, Wang Zhi-Hao, Shi Jinjin, Liu Junjie
Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, People's Republic of China.
Department of Neuroscience, Institute of Brain Science and Disease, Qingdao Medical College of Qingdao University, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266021, People's Republic of China.
Proc Natl Acad Sci U S A. 2024 Dec 24;121(52):e2403417121. doi: 10.1073/pnas.2403417121. Epub 2024 Dec 16.
Inflammatory bowel disease (IBD) is often associated with excessive inflammatory response and highly dysregulated gut microbiota. Traditional treatments utilize drugs to manage inflammation, potentially with probiotic therapy as an adjuvant. However, current standard practices often suffer from detrimental side effects, low bioavailability, and unsatisfactory therapeutic outcomes. Microbial complexes characterized by mutually beneficial symbiosis hold great promise for IBD therapy. Here, we aggregated sp. PCC6803 (Sp) with (BS) by biomimetic mineralization to form cyanobacteria-probiotics symbionts (ASp@BS), which reshaped a healthy immune system and gut microbiota in a murine model of acute colitis. The symbionts exhibited excellent tolerance to the harsh environment of the gastrointestinal tract. Importantly, probiotics within the symbionts created a local anaerobic environment to activate the [NiFe]-hydrogenase enzyme of cyanobacteria, facilitating the production of hydrogen gas (H) to persistently scavenge elevated reactive oxygen species and alleviate inflammatory factors. The resulting reduced inflammation improves the viability of the probiotics to efficiently regulate the gut microbiota and reshape the intestinal barrier functions. Our research elucidates that ASp@BS leverages the synergistic interaction between Sp and BS to create a therapeutic platform that addresses multiple aspects of IBD, offering a promising and comprehensive solution for IBD treatment.
炎症性肠病（IBD）通常与过度的炎症反应和高度失调的肠道微生物群有关。传统治疗方法使用药物来控制炎症，可能会辅以益生菌疗法。然而，目前的标准治疗方法往往存在有害的副作用、低生物利用度和不理想的治疗效果。以互利共生为特征的微生物复合体对IBD治疗具有很大的潜力。在这里，我们通过仿生矿化将聚球藻属PCC6803（Sp）与嗜热栖热菌（BS）聚集在一起，形成蓝藻-益生菌共生体（ASp@BS），它在急性结肠炎小鼠模型中重塑了健康的免疫系统和肠道微生物群。共生体对胃肠道的恶劣环境表现出优异的耐受性。重要的是，共生体内的益生菌创造了局部厌氧环境，以激活蓝藻的[NiFe]-氢化酶，促进氢气（H）的产生，持续清除升高的活性氧并减轻炎症因子。由此导致的炎症减轻提高了益生菌的活力，从而有效地调节肠道微生物群并重塑肠道屏障功能。我们的研究表明，ASp@BS利用Sp和BS之间的协同相互作用创建了一个治疗平台，该平台解决了IBD的多个方面问题，为IBD治疗提供了一个有前景的综合解决方案。
