Li Dongyue, Tao Huiling, Tan Xin, Ling Hao, Lu Yue, Zhang Huichao, Theany Sok, Xu Hongyu
Department of Gastroenterology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Front Microbiol. 2025 Aug 12;16:1643209. doi: 10.3389/fmicb.2025.1643209. eCollection 2025.
Ulcerative colitis (UC) is a recurrent inflammatory bowel disease affecting the colorectum, which remains a prominent research focus due to significant individual variations in clinical therapeutic outcomes. Fecal microbiota transplantation (FMT), as a therapeutic approach to restore intestinal homeostasis, has demonstrated favorable efficacy in UC management. However, given the characteristic alternating cycles of active and remission phases in UC, there remains a paucity of in-depth research regarding the optimal timing for FMT intervention. Concurrently, butyrate - a crucial microbial metabolite - ameliorates murine colitis through both direct and indirect mechanisms, while the therapeutic effectiveness of FMT in UC correlates closely with intestinal butyrate concentration.
This study established acute and chronic UC murine models and employed FMT and butyrate interventions to monitor dynamic alterations in gut microbiota and lymphocyte subsets. Through comprehensive analyses, we aimed to elucidate the interplay between gut microbiota and host immune mechanisms, identify the optimal therapeutic timing for UC interventions, and evaluate the mechanistic role of butyrate. These findings provide theoretical foundations for personalized microbiota-targeted therapies in UC.
Our findings demonstrate that gut microbiota and their metabolites exert therapeutic effects on murine acute/chronic colitis through modulation of the T helper cell 17 (Th17)/T regulatory cell (Treg) ratio. Specifically, the remission phase represents a more favorable window for intestinal homeostasis modulation, with combination therapy involving microbial metabolites exhibiting superior anti-inflammatory efficacy.
The maintenance of an appropriate Th17/Treg equilibrium during microbiota restoration demonstrates therapeutic advantages. Notably, butyrate synergistically enhances microbial therapeutic effects, providing experimental evidence for personalized modulation of gut ecosystems in inflammatory bowel disease management.
溃疡性结肠炎（UC）是一种影响结直肠的复发性炎症性肠病，由于临床治疗结果存在显著个体差异，它仍然是一个重要的研究焦点。粪便微生物群移植（FMT）作为一种恢复肠道稳态的治疗方法，在UC治疗中已显示出良好疗效。然而，鉴于UC具有活动期和缓解期交替的特点，关于FMT干预的最佳时机仍缺乏深入研究。同时，丁酸盐——一种关键的微生物代谢产物——通过直接和间接机制改善小鼠结肠炎，而FMT在UC中的治疗效果与肠道丁酸盐浓度密切相关。
本研究建立了急性和慢性UC小鼠模型，并采用FMT和丁酸盐干预来监测肠道微生物群和淋巴细胞亚群的动态变化。通过综合分析，我们旨在阐明肠道微生物群与宿主免疫机制之间的相互作用，确定UC干预的最佳治疗时机，并评估丁酸盐的作用机制。这些发现为UC中个性化的微生物群靶向治疗提供了理论基础。
我们的研究结果表明，肠道微生物群及其代谢产物通过调节辅助性T细胞17（Th17）/调节性T细胞（Treg）比例对小鼠急性/慢性结肠炎发挥治疗作用。具体而言，缓解期是调节肠道稳态更有利的窗口期，涉及微生物代谢产物的联合治疗具有更强的抗炎效果。
在微生物群恢复过程中维持适当的Th17/Treg平衡具有治疗优势。值得注意的是，丁酸盐可协同增强微生物治疗效果，为炎症性肠病管理中肠道生态系统的个性化调节提供了实验证据。
