Infection and Immunity Program, Biomedicine Discovery Institute, Department of Biochemistry, Monash University, Clayton, Australia.
Central Queensland University, School of Medical and Applied Sciences, Rockhampton, Australia.
Nat Immunol. 2017 May;18(5):552-562. doi: 10.1038/ni.3713. Epub 2017 Mar 27.
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.
肠道菌群失调可能是 1 型糖尿病发病机制的基础。在非肥胖型糖尿病（NOD）小鼠中，我们发现疾病的关键特征与血液和粪便中微生物代谢物乙酸盐和丁酸盐的浓度呈负相关。因此，我们用专门的饮食喂养 NOD 小鼠，这些饮食在细菌在结肠发酵后会释放大量的乙酸盐或丁酸盐。每种饮食都能提供高度的糖尿病保护，甚至在免疫耐受破坏后给予饮食也有保护作用。给小鼠喂食同时产生乙酸盐和丁酸盐的饮食可提供完全保护，这表明乙酸盐和丁酸盐可能通过不同的机制发挥作用。乙酸盐通过对 B 细胞及其扩大自身反应性 T 细胞群体的能力的影响，显著降低了淋巴组织中自身反应性 T 细胞的频率。含有丁酸盐的饮食增加了调节性 T 细胞的数量和功能，而产生乙酸盐和丁酸盐的饮食则增强了肠道完整性，并降低了血清中促炎细胞因子如 IL-21 的浓度。药用食品或代谢物可能代表一种有效和自然的方法，可以对抗导致 T 细胞依赖性自身免疫性疾病的许多免疫缺陷。
