Immunology and Environment, Life and Medical Sciences (LIMES) Institute, University of Bonn, Carl-Troll-Straße 31, 53115 Bonn, Germany.
Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsucho, Shinjuku-ku, Tokyo 162-8480, Japan.
Int J Mol Sci. 2020 Apr 30;21(9):3189. doi: 10.3390/ijms21093189.
A diet rich in vegetables and fruit is generally considered healthy because of a high content of phytochemicals, vitamins, and fiber. The phytochemical indole-3-carbinol (I3C), a derivative of glucobrassicin, is sold as a dietary supplement promising diverse health benefits. I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. Here, we investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition. For this, we used AhR repressor (AhRR)-reporter mice as a tool to study AhR activation in the intestine following dietary I3C-supplementation in comparison with AhR ligand-deprived diets, including a high fat diet. AhRR expression in intestinal immune cells was mainly driven by dietary AhR ligands and was independent of microbial metabolites. A lack of dietary AhR ligands caused enhanced susceptibility to dextran sodium sulfate (DSS)-induced colitis and correlated with the expansion of , whereas , , and were strongly reduced. I3C supplementation largely reverted this effect. Comparison of I3C-induced changes in microbiota composition using wild-type (WT), AhRR-deficient, and AhR-deficient mice revealed both AhR-dependent and -independent alterations in the microbiome. Overall, our study demonstrates that dietary AhR ligand supplementation has a profound influence on expression in intestinal immune cells as well as microbiota composition.
富含蔬菜和水果的饮食通常被认为是健康的，因为其含有丰富的植物化学物质、维生素和纤维。植物化学吲哚-3-甲醇（I3C）是葡萄糖异硫氰酸盐的衍生物，作为一种膳食补充剂出售，承诺具有多种健康益处。I3C 代谢物作为芳基烃受体（AhR）的配体发挥作用，AhR 是一种重要的环境多环芳烃化学传感器。在这里，我们研究了饮食 AhR 配体补充如何影响 AhR 靶基因表达和肠道微生物组组成。为此，我们使用 AhR 抑制剂（AhRR）-报告小鼠作为工具，研究在膳食 I3C 补充后，与 AhR 配体缺乏的饮食（包括高脂肪饮食）相比，AhR 在肠道中的激活情况。肠道免疫细胞中的 AhRR 表达主要受膳食 AhR 配体驱动，与微生物代谢物无关。缺乏膳食 AhR 配体导致对葡聚糖硫酸钠（DSS）诱导的结肠炎的易感性增加，并且与 的扩张相关，而 、 和 则强烈减少。I3C 补充在很大程度上逆转了这种效果。使用野生型（WT）、AhRR 缺陷型和 AhR 缺陷型小鼠比较 I3C 诱导的微生物组组成变化表明，微生物组存在 AhR 依赖和非依赖的改变。总体而言，我们的研究表明，饮食 AhR 配体补充对肠道免疫细胞中的 表达以及微生物组组成有深远影响。
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