College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province 050017, PR China.
Affiliated Hospital of Hebei University, College of Clinical Medicine, Hebei University, Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Baoding, Hebei Province 071000, PR China.
Biomed Pharmacother. 2024 Sep;178:117273. doi: 10.1016/j.biopha.2024.117273. Epub 2024 Aug 9.
The gut-brain axis mediates the interaction pathway between microbiota and opioid addiction. In recent years, many studies have shown that molecular hydrogen has therapeutic and preventive effects on various diseases. This study aimed to investigate whether molecular hydrogen could serve as pharmacological intervention agent to reduce risks of reinstatement of opioid seeking and explore the mechanism of gut microbiota base on animal experiments and human studies. Morphine-induced conditioned place preference (CPP) was constructed to establish acquisition, extinction, and reinstatement stage, and the potential impact of H on the behaviors related to morphine-induced drug extinction was determined using both free accessible and confined CPP extinction paradigms. The effects of morphine on microbial diversity and composition of microbiota, as well as the subsequent changes after H intervention, were assessed using 16 S rRNA gene sequencing. Short-Chain Fatty Acids (SCFAs) in mice serum were detected by gas chromatography-mass spectrometry (GC-MS). Meanwhile, we also conducted molecular hydrogen intervention and gut microbiota testing in opioid-addicted individuals. Our results revealed that molecular hydrogen could enhance the extinction of morphine-related behavior, reducing morphine reinstatement. Gut microbes may be a potential mechanism behind the therapeutic effects of molecular hydrogen on morphine addiction. Additionally, molecular hydrogen improved symptoms of depression and anxiety, as well as gut microbial features, in individuals with opioid addiction. This study supports molecular hydrogen as a novel and effective intervention for morphine-induced addiction and reveals the mechanism of gut microbiota.
肠道-大脑轴介导了微生物群和阿片类药物成瘾之间的相互作用途径。近年来，许多研究表明，分子氢对各种疾病具有治疗和预防作用。本研究旨在探讨分子氢是否可以作为药理学干预剂，降低阿片类药物寻求复吸的风险，并基于动物实验和人类研究探索肠道微生物群的机制。构建了吗啡诱导的条件位置偏好（CPP），以建立获得、消退和复吸阶段，并使用自由可及和受限 CPP 消退范式确定 H 对与吗啡诱导药物消退相关的行为的潜在影响。使用 16S rRNA 基因测序评估了吗啡对微生物多样性和微生物群落组成的影响，以及 H 干预后的后续变化。通过气相色谱-质谱联用（GC-MS）检测小鼠血清中的短链脂肪酸（SCFAs）。同时，我们还在阿片类药物成瘾者中进行了分子氢干预和肠道微生物群测试。我们的结果表明，分子氢可以增强与吗啡相关行为的消退，减少吗啡复吸。肠道微生物可能是分子氢治疗吗啡成瘾的潜在机制。此外，分子氢改善了阿片类药物成瘾者的抑郁和焦虑症状以及肠道微生物特征。这项研究支持分子氢作为一种新型有效的吗啡成瘾干预措施，并揭示了肠道微生物群的机制。
