Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique De Louvain, Brussels, Belgium.
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université Catholique De Louvain, Brussels, Belgium.
Gut Microbes. 2021 Jan-Dec;13(1):1959242. doi: 10.1080/19490976.2021.1959242.
Hypothalamic regulations of food intake are altered during obesity. The dopaminergic mesocorticolimbic system, responsible for the hedonic response to food intake, is also affected. Gut microbes are other key players involved in obesity. Therefore, we investigated whether the gut microbiota plays a causal role in hedonic food intake alterations contributing to obesity. We transferred fecal material from lean or diet-induced obese mice into recipient mice and evaluated the hedonic food intake using a food preference test comparing the intake of control and palatable diets (HFHS, High-Fat High-Sucrose) in donor and recipient mice. Obese mice ate 58% less HFHS during the food preference test ( < 0.0001) than the lean donors, suggesting a dysregulation of the hedonic food intake during obesity. Strikingly, the reduction of the pleasure induced by eating during obesity was transferable through gut microbiota transplantation since obese gut microbiota recipient mice exhibited similar reduction in HFHS intake during the food preference test (40% reduction as compared to lean gut microbiota recipient mice, < 0.01). This effect was associated with a consistent trend in modifications of dopaminergic markers expression in the striatum. We also pinpointed a highly positive correlation between HFHS intake and ( < 0.0001), which could represent a potential actor involved in hedonic feeding probably through the gut-to-brain axis. We further demonstrated the key roles played by gut microbes in this paradigm since depletion of gut microbiota using broad-spectrum antibiotics also altered HFHS intake during food preference test in lean mice. In conclusion, we discovered that gut microbes regulate hedonic aspects of food intake. Our data demonstrate that gut microbiota modifications associated with obesity participate in dysregulations of the reward and hedonic components of the food intake. These data provide evidence that gut microbes could be an interesting therapeutic target to tackle hedonic disorders related to obesity.
肥胖会改变摄食的下丘脑调节。负责摄食快感反应的多巴胺能中脑皮质边缘系统也受到影响。肠道微生物也是参与肥胖的另一个关键因素。因此，我们研究了肠道微生物是否在导致肥胖的快感食物摄入改变中起因果作用。我们将瘦鼠或饮食诱导肥胖鼠的粪便物质转移到受体鼠中，并通过食物偏好测试评估快感食物摄入，该测试比较了供体和受体鼠中对照和美味饮食（高糖高脂饮食，HFHS）的摄入量。在食物偏好测试中，肥胖鼠比瘦鼠供体少摄入 58%的 HFHS（<0.0001），这表明肥胖时快感食物摄入失调。引人注目的是，通过肠道微生物移植可以传递肥胖时进食快感的降低，因为肥胖肠道微生物受体鼠在食物偏好测试中也表现出 HFHS 摄入量的类似降低（与瘦肠道微生物受体鼠相比降低 40%，<0.01）。这种效应与纹状体中多巴胺标志物表达的一致变化趋势相关。我们还发现 HFHS 摄入量与（<0.0001）之间存在高度正相关，这可能代表了一个潜在的涉及快感喂养的因子，可能通过肠道-大脑轴起作用。我们进一步证明了肠道微生物在该模型中的关键作用，因为使用广谱抗生素耗尽肠道微生物也会改变瘦鼠在食物偏好测试中的 HFHS 摄入量。总之，我们发现肠道微生物调节食物摄入的快感方面。我们的数据表明，与肥胖相关的肠道微生物改变参与了食物摄入的奖励和快感成分的失调。这些数据提供了证据表明肠道微生物可能是一个有趣的治疗靶点，以解决与肥胖相关的快感障碍。
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