Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology “S. de Bellis”, IRCCS Research Hospital, 70013 Castellana Grotte, Italy.
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy.
Int J Mol Sci. 2022 Jan 20;23(3):1098. doi: 10.3390/ijms23031098.
Altered gut-brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT and 5-HT, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT, and 5-HT levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.
肠道-大脑通讯改变可能导致肠易激综合征的肠道功能障碍。具有神经保护作用的高脂肪、适量蛋白质、低碳水化合物生酮饮食（KD）可调节不同神经递质和神经营养因子的水平。本研究旨在评估 KD 对肠易激综合征（IBS）大鼠模型结肠和大脑中 5-HT、5-HT 和 5-HT 受体、5-HT 转运体 SERT、神经营养因子 BDNF 及其受体 TrkB 水平的影响。分析了新生期接受母体剥夺并随后接受标准饮食（IBS-Std）或 KD（IBS-KD）喂养 10 周的 Wistar 大鼠的样本。作为对照，研究了未暴露的大鼠（Ctrl-Std 和 Ctrl-KD）。与对照组相比，IBS-Std 大鼠的肠内 5-羟色胺能信号传导紊乱，表现为黏膜 5-HT 含量增加，SERT、5-HT 和 5-HT 水平降低。在大脑中，这些动物表现出 BDNF 受体 TrkB 的上调，作为对神经递质应激诱导减少的对抗反应。KD 表现出改善改变的 5-HT 和 BDNF 系统的双重作用。它下调了增加的黏膜 5-HT，而不影响转运体和受体水平。KD 改善了大脑 BDNF 水平并建立了负反馈，导致 TrkB 的代偿性下调以维持生理稳态。
