Laboratory of Innate Immunity, Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Front Immunol. 2019 Mar 11;10:277. doi: 10.3389/fimmu.2019.00277. eCollection 2019.
Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.
溃疡性结肠炎（UC）和克罗恩病（CD），统称为炎症性肠病（IBD），是由遗传、免疫、微生物和环境因素复杂相互作用引起的。肠道微生物组的失调越来越被认为与 IBD 有因果关系，并受到西方生活方式成分的强烈影响。与健康个体相比，发酵纤维并产生短链脂肪酸（SCFAs）的细菌在 IBD 患者的粘膜和粪便中通常减少。SCFAs，如乙酸盐、丙酸盐和丁酸盐，是维持肠道内稳态的重要代谢物。几项研究确实表明，在活动期 IBD 中粪便 SCFAs 水平降低。SCFAs 是肠道上皮细胞的重要燃料，已知可增强肠道屏障功能。然而，最近的发现表明，SCFAs，特别是丁酸盐，也具有重要的免疫调节功能。SCFAs 的吸收通过基质转运蛋白（如 MCT1 和 SMCT1）促进细胞代谢。此外，SCFAs 可以通过细胞表面 G 蛋白偶联受体（GPCR），如 GPR41、GPR43 和 GPR109A，传递信号，激活控制免疫功能的信号级联反应。转基因小鼠模型支持这些 GPCR 在控制肠道炎症中的关键作用。在这里，我们概述了微生物 SCFAs 的产生及其对肠道粘膜的影响，特别强调了它们与 IBD 的相关性。此外，我们讨论了 SCFAs 治疗 IBD 的潜在应用，无论是直接应用还是通过预或益生菌方法刺激 SCFAs 产生细菌。
