肠道菌群与健康、疾病和药物作用的影响

肠道菌群作为人体内一个复杂的微生态系统,在维持人体微生态的稳态中,肠道菌群在维持宿主生理功能具有上非常重要的作用,也对许多代谢性疾病、免疫性疾病以及肿瘤都有着密切的关系,且对于药物治疗合理安全有效具有重要意义。本文从正视存在人体的细菌的有益性和有害性、肠道菌群与健康和寿命、肠道菌群与疾病以及药物作用的影响等4方面分析和讨论。肠道菌群与不同类型药物的关系已经成为近些年的热点研究领域,本文分别讨论免疫治疗、化学药物、抗生素和中药的相关问题,希望为认识药物治疗过程、科学合理用药、认识药物作用机制、新药研究开发等研究有所参考。     

肠道菌群调控肥胖症脂质代谢机制的研究进展

肥胖是全球性健康问题,与多种代谢疾病相关。肠道菌群的特定改变是肥胖和肥胖相关的代谢疾病的重要特征之一。近年来,肠道菌群在肥胖及相关代谢疾病中的作用受到了越来越多的关注,被认为是肥胖潜在的治疗靶点。肠道菌群的组成丰富,其参与宿主脂质代谢机制复杂。本文介绍了肥胖发生发展过程中的代表性菌种,概述了肠道微生物调控宿主脂质代谢的潜在机制的研究进展,以期为基于肠道菌群为靶点的治疗手段和药物研发提供思路。     

肠道微生态与疾病、中药相互作用的研究进展

肠道菌群作为人体内一个复杂的微生态系统,并与宿主、环境构成了动态平衡的统一体。肠道菌群作为人体的"第二基因组"参与宿主新陈代谢和免疫调节,并与环境因子相互作用决定机体疾病与健康状态。本文就肠道菌群与各种疾病关系和中药对肠道微生态的调控以及其在肠菌代谢转化的研究进展进行综述,旨在认识中药治疗过程及作用机制,为合理用药、新药开发等研究提供参考。     

口服难吸收中药重塑肠道微生态干预代谢相关脂肪性肝病的研究进展

代谢相关脂肪性肝病（MAFLD）是多系统代谢紊乱的肝脏疾病,其发病机制的复杂性和治疗目标的多元化导致临床缺乏效果理想的药物。中药对防治肝脏疾病有很好的疗效,口服给药是最普遍的给药方式,药物不仅可以通过肠道与肠道菌群建立联系,而且经肠道细菌作用后可改善吸收差、生物利用度低的问题。然而,肠道微生态紊乱会导致机体免疫功能障碍并促进MAFLD的发生发展。因此,口服难吸收中药对肠道菌群的调节作用可能是治疗MAFLD的潜在靶点。从口服难吸收中药的药理作用、相关代谢、肠道菌群作用等不同角度总结了中药对MAFLD的治疗作用以及肠道菌群与MAFLD的联系,为研究中药、MAFLD和肠道菌群间的关系提供理论依据,为进一步研究中药治疗MAFLD奠定药效物质基础,为从肠道菌群角度研究中药治疗MAFLD的作用机制与靶点奠定基础。     

肠道菌群代谢药物研究进展

长期以来,由于肠道菌群本身的复杂性以及培养方法和分析技术的限制,肠道菌群在药物代谢和体内处置中的作用未得到应有的重视。近年来,随着技术的快速发展,围绕肠道菌群的大量研究将对肠道菌代谢和肠道菌-宿主共代谢的认识提高到前所未有的深度。肠道菌群不仅能够直接代谢许多药物,还通过宿主、菌群、药物之间复杂多维的相互作用间接改变药物代谢,从而影响个体对药物治疗的响应(效应、毒性、耐药性等)。肠道菌群结构及代谢功能受多种因素的影响。综述近期肠道菌群代谢药物研究领域的重要进展及研究趋势,以期推进精准治疗,促进药物发现及新的治疗策略的出现。     

益生元在药物递送系统中的研究进展

随着对肠道微生物研究的深入,肠道菌群对人类健康的影响受到关注,已成为当前生命科学和医学的研究热点,也被认为是疾病治疗的重要靶点。益生元可调节肠道菌群的组成和功能从而改善宿主健康。碳水化合物是最基本的益生元,其独特的理化性质及肠道菌调节能力可在实现药物靶向递送的同时又能促进肠道健康,从而对疾病的治疗发挥积极作用。本文对不同种类的益生元及其肠道菌调节机制进行了阐述,介绍了碳水化合物类益生元在药物递送系统中的研究进展,并对其应用前景进行展望,以期为相关研究提供参考。     

靶向肠道细菌呼吸及能量代谢调控炎症性肠病进程的治疗策略分析

肠道菌群失衡与多种宿主疾病密切相关,靶向肠道菌群中的代谢通路也成为当前防治宿主疾病的前沿策略和研究热点。炎症性肠病(inflammatory bowel disease, IBD)是一组病因不明的慢性进展性肠道炎症疾病。已有研究证实IBD的发生和发展与肠道菌群紊乱以及细菌的呼吸能量代谢之间存在一定联系,本文将结合最新的研究进展,对三者之间的关系进行整理分析,并提出调控肠道菌群呼吸与能量代谢,缓解宿主肠道炎症新的治疗策略。在IBD发生发展时,肠道菌群稳态失衡,其原因主要包括两方面:①宿主肠道炎症发生时,肠腔内氧气含量增加,致使兼性厌氧菌尤其是肠杆菌科细菌异常增殖,而绝对厌氧菌如厚壁菌门等细菌的生长则受到抑制;②肠道炎症副产物也会支持兼性厌氧菌的扩增,最终加剧肠道菌群失衡。失调的肠道菌群会进一步加剧肠道免疫稳态失衡,加重肠道炎症反应。最新研究证实可通过干扰细菌呼吸及能量代谢,抑制促炎细菌的异常增殖进而恢复菌群稳态,减轻IBD炎症反应。通过以上分析,提示可聚焦肠道菌群中的代谢通路,调控肠道细菌呼吸以及能量代谢,探索缓解宿主肠道炎症的治疗策略,对于IBD的临床治疗以及创新药物研究具有重要意义。     

睡眠剥夺与肠道菌群紊乱的关系及改善睡眠药物研发的探讨

肠道菌群作为人体内一个复杂的微生态系统,在维持宿主生理功能上起非常重要的作用,也与许多代谢性疾病、免疫性疾病有着密切的关系。分析睡眠剥夺与肠道菌群紊乱相关性研究的提出和再提出,综合分析肠道菌群紊乱与睡眠障碍的关系,为以肠道菌群为靶点的改善睡眠药物开发及防治方法与思路提供参考。     

短链脂肪酸:肠-器官轴调控疾病的信号使者

肠道菌群是一个复杂而动态的系统,对机体的健康至关重要。它作为机体的“第二基因组”,通过调节肠道神经、胃肠激素、肠屏障、肠道免疫和代谢与宿主重要脏器建立通讯轴,影响宿主的多种生理功能。短链脂肪酸作为肠道菌群的重要代谢产物,在机体的免疫、代谢、内分泌及信号传导等方面都有重要作用,是肠-器官轴上的重要通讯物质。本文总结了肠-肝/脑/肾/肺轴与疾病的互作关系,并重点探讨了短链脂肪酸在这种互作关系中的作用及机制,为相关疾病的治疗提供新思路。     

常见药物毒性相关的肠道菌群研究进展

肠道菌群在物质信息传递、代谢等方面发挥重要作用，随着生物技术的进步，人们对肠道菌群与宿主健康的关系有了进一步的认识。近年来的研究发现，肠道菌群与某些药物毒性存在相关性。文章总结了药物肝毒性、肾毒性、神经毒性和生殖及幼龄毒性相关的肠道菌群研究成果，以期为药物毒理研究提供参考。     

药物基于“肠-脑”通路的研究进展

肠道菌群是由诸多共生及致病微生物组成的复杂而动态的群落,并与宿主紧密合作.近年来,越来越多的证据支持“肠-脑”轴理论,肠道菌群与神经精神疾病之间的联系逐步被发现.由于神经精神疾病治疗药物大多经口服后进入肠道,使得其与肠道菌群可能产生更广泛的相互作用.多项研究表明该类药物可改变肠道菌群的组成和功能,同时肠道菌群也会参与药...     

肠道菌群相关的抗抑郁治疗研究进展

目的 介绍肠道菌群与抑郁症的病理机制以及相关治疗的研究进展,为后续以肠道菌为靶点的抗抑郁药物的研发提供帮助。方法 查阅近年来肠道菌群与抑郁症方面的33篇中英文文献进行分类总结,从肠道菌群的门、科、属水平的角度探讨了抑郁状态下肠道菌群多样性的变化,从分子水平上阐述了肠道菌与抑郁症发病机制之间的关系,总结现有相关研究,进一步探索以肠道菌群为靶点进行药物研发治疗的可行性。结果 肠道菌紊乱与抑郁症之间相互作用,现有益生菌等生物制剂可通过改善肠道菌群病理状态下的紊乱对抑郁症治疗起到缓解作用。结论 肠道菌群失调与抑郁的发生密切相关,以肠道菌为靶点的相关药物研发治疗,可能成为治疗抑郁症的新途径。     

Mechanisms of gastrointestinal microflora on drug metabolism in clinical practice

Considered as an essential “metabolic organ”, intestinal microbiota plays a key role in human health and the predisposition to diseases. It is an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract. Since the 20th century, researches have showed that intestinal microbiome possesses a variety of metabolic activities that are able to modulate the fate of more than 30 approved drugs and immune checkpoint inhibitors. These drugs are transformed to bioactive, inactive, or toxic metabolites by microbial direct action or host-microbial co-metabolism. These metabolites are responsible for therapeutic effects exerted by these drugs or side effects induced by these drugs, even for death. In view of the significant effect on the drugs metabolism by the gut microbiota, it is pivotal for personalized medicine to explore additional drugs affected by gut microbiota and their involved strains for further making mechanism clear through suitable animal models. This review mainly focus on specific mechanisms involved, with reference to the current literature about drugs metabolism by related bacteria or its enzymes available.     

Gut microbiota in pancreatic diseases: possible new therapeutic strategies

Pancreatic diseases such as pancreatitis, type 1 diabetes and pancreatic cancer impose substantial health-care costs and contribute to marked morbidity and mortality. Recent studies have suggested a link between gut microbiota dysbiosis and pancreatic diseases; however, the potential roles and mechanisms of action of gut microbiota in pancreatic diseases remain to be fully elucidated. In this review, we summarize the evidence that supports relationship between alterations of gut microbiota and development of pancreatic diseases, and discuss the potential molecular mechanisms of gut microbiota dysbiosis in the pathogenesis of pancreatic diseases. We also propose current strategies toward gut microbiota to advance a developing research field that has clinical potential to reduce the cost of pancreatic diseases.     

药物微生物组学:肠道微生物与个体化用药

药物的安全性与有效性是临床治疗中的关键问题,大量研究表明,人体微生物与药物的疗效、不良反应等显著相关。随着人类微生物组计划的实施,药物微生物组学成为当前生命科学和医学的研究热点。药物微生物组学是药物基因组学的重要扩展和补充,致力于研究药物与微生物之间的相互作用及其与药物效应之间的关系。药物微生物组学研究尚处于起步阶段,其发展将为个体化医学和精准医疗提供必要参考。简介药物微生物组学的发展,并对肠道菌群与个体化用药的国内外研究现状进行综述。     

Gut microbiota modulates drug pharmacokinetics

Abstract

Gut microbiota, one of the determinants of pharmacokinetics, has long been underestimated. It is now generally accepted that the gut microbiota plays an important role in drug metabolism during enterohepatic circulation either before drug absorption or through various microbial enzymatic reactions in the gut. In addition, some drugs are metabolized by the intestinal microbiota to specific metabolites that cannot be formed in the liver. More importantly, metabolizing drugs through the gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs. Therefore, understanding intestinal flora-mediated drug metabolism is critical to interpreting changes in drug pharmacokinetics. Here, we summarize the effects of gut microbiota on drug pharmacokinetics, and propose that the influence of intestinal flora on pharmacokinetics should be organically related to the therapeutic effects and side effects of drugs. More importantly, we could rationally perform the strategy of intestinal microflora-mediated metabolism to design drugs.     

Impact of gut microbiota on drug metabolism: an update for safe and effective use of drugs

The intestinal mucosa and liver have long been considered as the main sites of drug metabolism, and the contribution of gut microbiota to drug metabolism has been under-estimated. However, it is now generally accepted that the gut microbiota plays an important role in drug metabolism prior to drug absorption or during enterohepatic circulation via various microbial enzymatic reactions in the intestine. Moreover, some drugs are metabolized by gut microbiota to specific metabolite(s) that cannot be formed in the liver. More importantly, the metabolism of drugs by gut microbiota prior to absorption can alter the systemic bioavailability of certain drugs. Therefore, understanding drug metabolism by gut microbiota is critical for explaining changes in the pharmacokinetics of drugs, which may cause significant alterations in drug-induced pharmacodynamics and toxicities. In this review, we describe recent progress with regard to the role of metabolism by gut microbiota in some drug-induced alterations of either pharmacological or toxicological effects to emphasize the clinical importance of gut microbiota for safe and effective use of drugs.