Fang Jian, Zhang ZhuangWei, Cheng Yinyin, Yang Haitao, Zhang Hui, Xue Zhe, Lu Songtao, Dong Yichen, Song Chunyan, Zhang Xiaohong, Zhou Yuping
Department of Preventive Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, People's Republic of China.
College of Medicine, Shaoxing University, 508 Huancheng Road, Shaoxing, Zhejiang Province, 312000, People's Republic of China.
Food Funct. 2022 Apr 20;13(8):4399-4420. doi: 10.1039/d1fo03815j.
: Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon with a continuously remitting and relapsing course. Its etiology is closely related to abnormal interactions between host and gut microbiota. The mucus barrier lining the gastrointestinal tract is necessary to coordinate host and gut microbiota interaction by nourishing and modulating the microbiota. Differential effects of the anti-inflammatory fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on UC progression in mice were firstly addressed by our previous work; here, the mechanism for their respective effects were further uncovered from host-microbiome crosstalk based on mucus barrier modulation to pave the way for UC therapy. : Assessment of the disease activity index and histopathology score was conducted in mice with dextran sodium sulfate (DSS)-induced colitis pre-treated with different doses of EPA and DHA. Mucin generation, glycosylation and secretion were evaluated by a combination of electron microscopy, specific mucous staining, and qPCR. Western blotting was used to analyze the underlying molecular events. Fecal short chain fatty acids were detected using gas chromatography, and the gut microbial composition was analyzed using 16S rRNA sequencing. : Compared with DHA, the more potent inhibitory effect of high dose EPA on DSS-induced colitis was reconfirmed, which was underlain by a reinforced mucus layer as indicated by increased mucin granule release, mucus layer stratification and markedly upregulated expression of the key modulators involved in goblet cell differentiation. In turn a remarkably enhanced mucus barrier in the EPA group functioned to modulate the gut microbiome, as demonstrated by the enriched abundance of the phylum and mucin-degrading bacterium producing acetic and propionic acids. : EPA and DHA differentially coordinate the interaction between the host and the gut microbiota and relieve mucus barrier disruption in DSS-induced colitis. EPA may develop into a promising adjunctive therapy for UC.
溃疡性结肠炎（UC）是一种结肠的慢性炎症性疾病，病程呈持续缓解和复发状态。其病因与宿主和肠道微生物群之间的异常相互作用密切相关。胃肠道内衬的黏液屏障对于通过滋养和调节微生物群来协调宿主与肠道微生物群的相互作用至关重要。我们之前的工作首次探讨了抗炎脂肪酸二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）对小鼠UC进展的不同影响；在此，基于黏液屏障调节从宿主-微生物组相互作用中进一步揭示了它们各自作用的机制，为UC治疗铺平道路。
对用不同剂量的EPA和DHA预处理的葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠进行疾病活动指数和组织病理学评分评估。通过电子显微镜、特异性黏液染色和定量聚合酶链反应（qPCR）相结合的方法评估黏蛋白的生成、糖基化和分泌。采用蛋白质免疫印迹法分析潜在的分子事件。使用气相色谱法检测粪便短链脂肪酸，并使用16S核糖体RNA（rRNA）测序分析肠道微生物组成。
与DHA相比，高剂量EPA对DSS诱导的结肠炎具有更强的抑制作用，这一作用的基础是黏液层增强，表现为黏蛋白颗粒释放增加、黏液层分层以及杯状细胞分化相关关键调节因子的表达显著上调。反过来，EPA组显著增强的黏液屏障起到了调节肠道微生物群的作用，表现为产生乙酸和丙酸的门和黏蛋白降解菌的丰度增加。
EPA和DHA以不同方式协调宿主与肠道微生物群之间的相互作用，并缓解DSS诱导的结肠炎中黏液屏障的破坏。EPA可能发展成为一种有前景的UC辅助治疗方法。
