Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
GenPhySE, Université de Toulouse, INRAE, ENVT, 31320, Castanet Tolosan, France.
J Nutr. 2021 Jun 1;151(6):1507-1516. doi: 10.1093/jn/nxab032.
The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.
The aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD.
Eight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4-5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5 mM, n ≥6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed.
Indole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motif chemokine ligand 2 (Cxcl2); 3.3- compared with 5.0-fold, and 2.4- compared with 3.3-fold of control ob/+ mice, respectively, P < 0.05], and in macrophage activation [Cd68, integrin subunit α X (Itgax); 2.1- compared with 2.5-fold, and 5.0- compared with 6.4-fold of control ob/+ mice, respectively, P < 0.01] as well as markers of hepatic damage (alaninine aminotransferase; -32%, P < 0.001) regardless of genotype in experiment 1. Indole had no effect on hepatic inflammation in mice fed the LF or HF diet in experiment 2. Indole did not change hepatic lipid content, anxiety-like behavior, or inflammation in the ileum, adipose tissue, and brain in experiment 1.
Our results support the efficacy of indole to reduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier.
肠道微生物群在非酒精性脂肪性肝病（NAFLD）的发生中起作用，特别是通过产生生物活性代谢物。吲哚是色氨酸的细菌代谢产物，已被提出作为调节炎症、代谢和行为的关键代谢物。
本研究旨在模拟肠道细菌吲哚产生的上调，并在 2 种 NAFLD 模型中体内评估其潜在作用。
将 8 周龄瘦素缺乏型雄性 ob/ob 与对照 ob/+ 小鼠（实验 1）相比，以及 4-5 周龄 C57BL/6JRj 雄性小鼠给予低脂（LF，10 kJ%）与高脂（HF，60 kJ%）饮食（实验 2）相比，分别给予普通水或补充生理剂量吲哚（0.5 mM，每组 n≥6）3 周和 3 d。评估处理对肝脏、肠道、脂肪组织、大脑和行为的影响。
吲哚降低了肝脏中参与炎症的基因的表达[C-C 基序趋化因子配体 2（Ccl2），C-X-C 基序趋化因子配体 2（Cxcl2）；分别与对照 ob/+ 小鼠相比，为 3.3-和 2.4-倍，P<0.05]，以及巨噬细胞激活[Cd68，整合素亚基α X（Itgax）；分别与对照 ob/+ 小鼠相比，为 2.1-和 5.0-倍，P<0.01]以及肝损伤标志物（丙氨酸氨基转移酶；-32%，P<0.001），而与实验 1 中的基因型无关。吲哚对实验 2 中 LF 或 HF 饮食喂养的小鼠的肝脏炎症没有影响。吲哚在实验 1 中没有改变肝脏脂质含量、焦虑样行为或回肠、脂肪组织和大脑的炎症。
我们的结果支持吲哚降低 ob/ob 小鼠肝损伤和相关炎症反应和巨噬细胞激活的功效。这些变化似乎归因于吲哚对肝脏的直接作用，而不是通过对脂肪组织或肠道屏障的作用。
