Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder
Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder
复制标题
肠道微生物群引发的β-羟基丁酸代谢变化与酒精使用障碍患者的社交能力改变及抑郁相关
DOI：
10.1016/j.celrep.2020.108238
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发表时间：
2020-10-13
期刊：
影响因子：
8.8
通讯作者：
Delzenne, Nathalie M.
中科院分区：
文献类型：
--
作者：
Leclercq, Sophie;Le Roy, Tiphaine;Delzenne, Nathalie M.
酒精使用障碍（AUD）患者存在重要的情感、认知和社交障碍。肠道微生物群最近被证明可以调节大脑功能和行为，但缺乏令人信服的证据证明其在AUD中的作用。在这里，我们表明肠道生态失调与代谢改变有关，代谢改变会影响酒精成瘾的行为（抑郁、社交）和神经生物学（髓鞘形成、神经传递、炎症）过程。通过将AUD患者的肠道微生物群移植到小鼠身上，我们指出，特定细菌属产生的乙醇和脂肪分解的减少与肝脏合成β -羟基丁酸酯（BHB）的降低有关，从而阻止了BHB的神经保护作用。我们在解毒AUD患者中证实了这些结果，在这些患者中，我们观察到粪便中持续产生乙醇，以及低血浆BHB水平与社交障碍、抑郁或脑白质改变之间的相关性。
Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of beta-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations.