Sun Xinyu, Yun Long, Xie Keming, Liu Renhui, Ren Xinyue, Zeng Bokun, Cao Xudong, Li Zhi, Zhou Guihao, Liu Bang, Peng Luo, Yuan Lihong
School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
Huzhou Key Laboratory of Translational Medicine, First Affiliated Hospital of Huzhou University, Huzhou, China.
Front Microbiol. 2025 Jan 7;15:1507979. doi: 10.3389/fmicb.2024.1507979. eCollection 2024.
Gut microbiota dysbiosis significantly impacts ulcerative colitis (UC) progression and exacerbation. Probiotics show promise in UC management. This study evaluated the effects of different doses of LV149, an aquatic-derived probiotic, on gut injury repair in male C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and investigated the underlying mechanisms.
UC was induced by allowing mice free access to a 3% DSS solution for 7 days, with concurrent daily oral gavage of either a low (LV149-L, 1 × 10 CFU/day/mouse) or high (LV149-H, 1 × 10 CFU/day/mouse) dose of LV149. The effects were assessed through physiological parameters, intestinal barrier integrity, inflammation, gut microbiota composition, and transcriptomic changes.
LV149 significantly improved pathological symptoms, including weight loss and disease activity index (DAI), and reduced colon shortening in a dose-dependent manner and inflammatory damage. The intervention also restored gut barrier function by upregulating mucins, goblet cell counts, and tight junction proteins (ZO-1, occludin, and claudin-1) in colonic tissue, along with reducing serum lipopolysaccharide (LPS) levels. Notably, only the LV149-H significantly decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while both doses increased the expression of the anti-inflammatory cytokine IL-10 in a dose-dependent in colonic tissue. LV149 further modulated the gut microbiota, increasing beneficial bacteria and reducing pathogenic populations. Transcriptomic analysis indicated that LV149-L may exert gut repair effects via the IL-17 signaling pathway, whereas LV149-H appears to act through the JAK-STAT signaling pathway.
This study demonstrated that LV149, particularly at a higher dose, effectively mitigated DSS-induced colonic injury by modulating gut microbiota, enhancing gut barrier integrity, and reducing inflammation. The dose-dependent effects underscored LV149-H's potential as a therapeutic agent for UC due to its stronger anti-inflammatory properties and gut-protective effects.
肠道微生物群失调对溃疡性结肠炎（UC）的进展和恶化有显著影响。益生菌在UC管理中显示出前景。本研究评估了不同剂量的水生来源益生菌LV149对葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）雄性C57BL/6小鼠肠道损伤修复的影响，并研究了其潜在机制。
通过让小鼠自由饮用3% DSS溶液7天诱导UC，同时每日口服低剂量（LV149-L，1×10⁸CFU/天/小鼠）或高剂量（LV149-H，1×10⁹CFU/天/小鼠）的LV149。通过生理参数、肠道屏障完整性、炎症、肠道微生物群组成和转录组变化评估效果。
LV149显著改善了病理症状，包括体重减轻和疾病活动指数（DAI），并以剂量依赖方式减少了结肠缩短和炎症损伤。该干预还通过上调结肠组织中的粘蛋白、杯状细胞计数和紧密连接蛋白（ZO-1、闭合蛋白和claudin-1）恢复了肠道屏障功能，同时降低了血清脂多糖（LPS）水平。值得注意的是，只有LV149-H显著降低了促炎细胞因子TNF-α、IL-1β和IL-6的表达，而两种剂量均以剂量依赖方式增加了结肠组织中抗炎细胞因子IL-10的表达。LV149进一步调节了肠道微生物群，增加了有益细菌并减少了致病菌群。转录组分析表明，LV149-L可能通过IL-17信号通路发挥肠道修复作用，而LV149-H似乎通过JAK-STAT信号通路起作用。
本研究表明，LV149，特别是高剂量时，通过调节肠道微生物群、增强肠道屏障完整性和减少炎症，有效减轻了DSS诱导的结肠损伤。剂量依赖性效应突出了LV149-H作为UC治疗剂的潜力，因为它具有更强的抗炎特性和肠道保护作用。
