目的 根据“三因制宜”理论在疾病发生发展中的重要作用，结合我国岭南地区独特的“湿热”饮食环 境，探讨“湿热型”内外环境对溃疡性结肠炎（UC）的影响及其潜在机制，特别是肠道菌群在诱导 UC 中的调 节作用。方法 采取受饮食环境干预的葡聚糖硫酸钠（DSS）诱导的 UC 小鼠模型。通过暴露于高温和高湿的外 环境，以及高糖高脂肪的饮食和饮酒的内环境模拟湿热环境对 UC 发展的影响。为了评估这些因素的影响，收 集小鼠的生物样本来客观分析“湿热”因素的评价指标，如炎症因子、水通道蛋白、血脂指数和肠道菌群的组 成。此外，该研究利用粪菌移植技术（FMT）揭示肠道菌群在“湿热”饮食环境影响中的作用。结果 “湿热型” 内外环境影响下 UC 小鼠 DAI 评分增加，结肠长度缩短，上皮结构破坏，促炎因子水平升高，血脂代谢和水通 道蛋白表达病理性改变。16SrRNA 测序结果表明肠道菌群中变形菌门丰度增加而厚壁菌门丰度减少。粪菌移 植实验证实，“湿热”的内外环境对肠道菌群的负向调节是 UC 恶化的重要机制。结论 “湿热”的内外环境通 过调节肠道菌群，从而影响脂质和水液代谢以及炎症反应，使 DSS 诱导的 UC 恶化。这些发现为 UC 发生、发 展变化中与饮食环境之间的病理生理相互作用提供了更清晰的认识。

Objective To investigate the influence of "damp-heat typed" internal and external environments on ulcerative colitis （UC） and its underlying mechanisms， particularly the regulatory role of gut microbiota in UC pathogenesis，guided by the "treatment in accordance with three categories of etiological factors" theory and combined with the unique "damp-heat typed" dietary environment in China's Lingnan region. Methods A dextran sulfate sodium （DSS）-induced UC mouse model was established under dietary and environmental interventions. External damp-heat conditions （high temperature and humidity） and internal damp-heat factors （high-sugar， high-fat diet with alcohol intake） were simulated to replicate the effects of a "damp-heat" environment on UC progression. Biological samples were collected to analyze objective indicators， including inflammatory cytokines， aquaporins， lipid profiles， and gut microbiota composition. Fecal microbiota transplantation （FMT） was employed to elucidate the role of gut microbiota in mediating the effects of the "damp-heat" dietary environment. Results Under the "damp-heat typed" environments， UC mice exhibited elevated disease activity index （DAI） scores，shortened colon length，disrupted epithelial structure， increased proinflammatory cytokine levels， pathological alterations in lipid metabolism， and dysregulated aquaporin expression. 16SrRNA sequencing revealed an increased abundance of Proteobacteria and decreased Firmicutes in the gut microbiota. FMT experiments confirmed that the "damp-heat typed" environments exacerbated UC through detrimental modulation of gut microbiota. Conclusion The "damp-heat" internal and external environments aggravate DSS-induced UC by reshaping gut microbiota， thereby disrupting lipid/fluid metabolism and amplifying inflammatory responses. These findings provide a clearer understanding of the pathophysiological interplay between dietary environments and UC progression.

R285.5

国家自然科学基金项目（82274227）；广东省基础与应用基础研究基金项目（2022A1515140124，2022A1515140011，2023A1515220035， 2023A1515140115）；中山市中医药传承创新发展科研专项（2024B3003）。