Li Chunjia, Wang Miao, Duan Lixiao, Xin Jinge, Ni Xueqin, Zeng Dong, Wu Bangyuan
Key Laboratory of the Ministry of Education for Wildlife and Plant Resources Conservation in Southwest China, College of Life Sciences, China West Normal University, Nanchong, Sichuan, China.
College of Veterinary Medicine, Animal Microecology Institute, Sichuan Agricultural University, Chengdu, China.
Probiotics Antimicrob Proteins. 2025 Sep 9. doi: 10.1007/s12602-025-10712-1.
Enterotoxigenic Escherichia coli (ETEC) is a prevalent intestinal pathogen that significantly impacts both human and animal health. G83, isolated from giant panda feces, has demonstrated notable probiotic properties. In this study, C57BL/6 J mice were randomly divided into Control, ETEC, and G83 groups. Experimental included monitoring body weight, assessing fecal occult blood, histopathological examination of ileal tissues, and quantification of antioxidant markers (SOD, T-AOC, MDA) in ileal tissues. Furthermore, real-time quantitative PCR was utilized to determine mRNA expression levels of inflammatory cytokines (TNF-α, IL-17, IL-10), tight junction proteins (Claudin, ZO-1, Occludin), mucin (Muc2), and lysozyme (Lyz-1). Transcriptomic bioinformatics analysis and 16S rRNA sequencing were integrated to characterize host gene expression profiles and gut microbial compositional dynamics, respectively. The results revealed that G83 alleviated ETEC-induced weight loss, reduced fecal occult blood, and mitigated ileal structural injuries. Additionally, G83 significantly enhanced intestinal antioxidant capacity by increasing T-AOC and SOD levels. Mechanistically, G83 downregulated pro-inflammatory cytokines TNF-α and IL-17 and the levels of Muc2 and Lyz1, while upregulating the expression of tight junction proteins ZO-1, Claudin, and Occludin. Transcriptomic analysis suggests that ETEC triggers inflammasome activation and initiates inflammatory responses by significantly upregulating Aim2. Conversely, G83 exerts protective effects by modulating the immune regulatory network-specifically, by significantly downregulating C3 expression to activate the complement system and participating in mucosal immune remodeling. Enrichment analysis reveals that G83 alleviates ETEC-induced intestinal inflammation primarily by inhibiting the NF-κB pathway and enhancing the intestinal IgA immune network. Additionally, 16S rRNA analysis indicates that G83 may improve ETEC-induced alterations in microbial community structure by increasing the abundance of beneficial bacteria (e.g., Lactobacillus), thereby further ameliorating impairment of intestinal microbial barrier function in mice. These findings provide a scientific basis for using G83 to ameliorate ETEC-mediated intestinal inflammation.
产肠毒素大肠杆菌（ETEC）是一种常见的肠道病原体，对人类和动物健康都有重大影响。从大熊猫粪便中分离出的G83已显示出显著的益生菌特性。在本研究中，将C57BL/6 J小鼠随机分为对照组、ETEC组和G83组。实验内容包括监测体重、评估粪便潜血、对回肠组织进行组织病理学检查以及对回肠组织中的抗氧化标志物（超氧化物歧化酶、总抗氧化能力、丙二醛）进行定量分析。此外，利用实时定量PCR来测定炎性细胞因子（肿瘤坏死因子-α、白细胞介素-17、白细胞介素-10）、紧密连接蛋白（闭合蛋白、闭锁小带蛋白1、闭合小环蛋白）、黏蛋白（Muc2）和溶菌酶（Lyz - 1）的mRNA表达水平。整合转录组生物信息学分析和16S rRNA测序，分别以表征宿主基因表达谱和肠道微生物组成动态变化。结果显示，G83减轻了ETEC诱导的体重减轻，减少了粪便潜血，并减轻了回肠结构损伤。此外，G83通过提高总抗氧化能力和超氧化物歧化酶水平，显著增强了肠道抗氧化能力。从机制上讲，G83下调促炎细胞因子肿瘤坏死因子-α和白细胞介素-17以及Muc2和Lyz1的水平，同时上调紧密连接蛋白闭锁小带蛋白1、闭合蛋白和闭合小环蛋白的表达。转录组分析表明，ETEC通过显著上调Aim2触发炎性小体激活并引发炎症反应。相反，G83通过调节免疫调节网络发挥保护作用，具体而言，通过显著下调C3表达来激活补体系统并参与黏膜免疫重塑。富集分析表明，G83主要通过抑制核因子-κB途径和增强肠道IgA免疫网络来减轻ETEC诱导的肠道炎症。此外，16S rRNA分析表明，G83可能通过增加有益菌（如乳酸杆菌）的丰度来改善ETEC诱导的微生物群落结构改变，从而进一步改善小鼠肠道微生物屏障功能的损害。这些发现为使用G83改善ETEC介导的肠道炎症提供了科学依据。
