The gut microbiome modulates neurochemical function and behavior and has been implicated in numerous central nervous system (CNS) diseases, including developmental, neurodegenerative, and psychiatric disorders. Substance use disorders (SUDs) remain a serious threat to the public well-being, yet gut microbiome involvement in drug abuse has received very little attention. Studies of the mechanisms underlying SUDs have naturally focused on CNS reward circuits. However, a significant body of research has accumulated over the past decade that has unwittingly provided strong support for gut microbiome participation in drug reward. β-Lactam antibiotics have been employed to increase glutamate transporter expression to reverse relapse-induced release of glutamate. Sodium butyrate has been used as a histone deacetylase inhibitor to prevent drug-induced epigenetic alterations. High-fat diets have been used to alter drug reward because of the extensive overlap of the circuitry mediating them. This review article casts these approaches in a different light and makes a compelling case for gut microbiome modulation of SUDs. Few factors alter the structure and composition of the gut microbiome more than antibiotics and a high-fat diet, and butyrate is an endogenous product of bacterial fermentation. Drugs such as cocaine, alcohol, opiates, and psychostimulants also modify the gut microbiome. Therefore, their effects must be viewed on a complex background of cotreatment-induced dysbiosis. Consideration of the gut microbiome in SUDs should have the beneficial effects of expanding the understanding of SUDs and aiding in the design of new therapies based on opposing the effects of abused drugs on the host’s commensal bacterial community.

中文翻译：

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肠道微生物调节物质使用障碍的证据：隐藏在众目睽睽之下


肠道微生物组调节神经化学功能和行为，并与许多中枢神经系统 (CNS) 疾病有关，包括发育性疾病、神经退行性疾病和精神疾病。药物滥用障碍（SUD）仍然对公众福祉构成严重威胁，但肠道微生物组与药物滥用的关系却很少受到关注。对 SUD 潜在机制的研究自然集中在中枢神经系统奖赏回路上。然而，过去十年积累的大量研究无意中为肠道微生物参与药物奖励提供了强有力的支持。 β-内酰胺抗生素已被用来增加谷氨酸转运蛋白的表达，以逆转复发引起的谷氨酸释放。丁酸钠已被用作组蛋白脱乙酰酶抑制剂，以防止药物诱导的表观遗传改变。高脂肪饮食已被用来改变药物奖励，因为介导它们的电路广泛重叠。这篇综述文章从不同的角度阐述了这些方法，并为 SUD 的肠道微生物组调节提供了令人信服的案例。很少有因素比抗生素和高脂肪饮食更能改变肠道微生物组的结构和组成，而丁酸盐是细菌发酵的内源产物。可卡因、酒精、阿片类药物和精神兴奋剂等药物也会改变肠道微生物组。因此，必须在共同治疗引起的生态失调的复杂背景下看待它们的影响。在 SUD 中考虑肠道微生物组应该具有有益的作用，可以扩大对 SUD 的理解，并有助于设计基于反对滥用药物对宿主共生细菌群落影响的新疗法。