Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
Psychopharmacology (Berl). 2019 May;236(5):1513-1530. doi: 10.1007/s00213-019-05232-0. Epub 2019 Apr 14.
Pathological substance use disorders represent a major public health crisis with limited effective treatment options. While much work has been done to understand the neuronal signaling networks and intracellular signaling cascades associated with prolonged drug use, these studies have yielded few successful treatment options for substance use disorders. In recent years, there has been a growing interest to explore interactions between the peripheral immune system, the gut microbiome, and the CNS. In this review, we will present a summary of existing evidence, suggesting a potential role for gut dysbiosis in the pathogenesis of substance use disorders. Clinical evidence of gut dysbiosis in human subjects with substance use disorder and preclinical evidence of gut dysbiosis in animal models of drug addiction are discussed in detail. Additionally, we examine how changes in the gut microbiome and its metabolites may not only be a consequence of substance use disorders but may in fact play a role in mediating behavioral response to drugs of abuse. While much work still needs to be done, understanding the interplay of gut microbiome in substance use disorders may offer a promising avenue for future therapeutic development.
病理性物质使用障碍是一种主要的公共健康危机，目前有效的治疗选择有限。尽管已经开展了大量工作来了解与长期药物使用相关的神经元信号网络和细胞内信号级联，但这些研究对物质使用障碍的治疗选择收效甚微。近年来，人们越来越有兴趣探索外周免疫系统、肠道微生物群和中枢神经系统之间的相互作用。在这篇综述中，我们将总结现有的证据，表明肠道菌群失调在物质使用障碍发病机制中的潜在作用。详细讨论了物质使用障碍患者的临床肠道菌群失调证据和药物成瘾动物模型中的临床前肠道菌群失调证据。此外，我们还研究了肠道微生物组及其代谢物的变化如何不仅可能是物质使用障碍的结果，而且实际上可能在介导对滥用药物的行为反应中发挥作用。虽然仍有许多工作要做，但了解肠道微生物组在物质使用障碍中的相互作用可能为未来的治疗开发提供一个有希望的途径。
