Maseda Damian, Ricciotti Emanuela
Department of Microbiology, University of Pennsylvania, Philadelphia, PA, United States.
Department of Systems Pharmacology and Translational Therapeutics, and Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, United States.
Front Pharmacol. 2020 Aug 7;11:1153. doi: 10.3389/fphar.2020.01153. eCollection 2020.
Nonsteroidal anti-inflammatory drugs (NSAID)s relieve pain, inflammation, and fever by inhibiting the activity of cyclooxygenase isozymes (COX-1 and COX-2). Despite their clinical efficacy, NSAIDs can cause gastrointestinal (GI) and cardiovascular (CV) complications. Moreover, NSAID use is characterized by a remarkable individual variability in the extent of COX isozyme inhibition, therapeutic efficacy, and incidence of adverse effects. The interaction between the gut microbiota and host has emerged as a key player in modulating host physiology, gut microbiota-related disorders, and metabolism of xenobiotics. Indeed, host-gut microbiota dynamic interactions influence NSAID disposition, therapeutic efficacy, and toxicity. The gut microbiota can directly cause chemical modifications of the NSAID or can indirectly influence its absorption or metabolism by regulating host metabolic enzymes or processes, which may have consequences for drug pharmacokinetic and pharmacodynamic properties. NSAID itself can directly impact the composition and function of the gut microbiota or indirectly alter the physiological properties or functions of the host which may, in turn, precipitate in dysbiosis. Thus, the complex interconnectedness between host-gut microbiota and drug may contribute to the variability in NSAID response and ultimately influence the outcome of NSAID therapy. Herein, we review the interplay between host-gut microbiota and NSAID and its consequences for both drug efficacy and toxicity, mainly in the GI tract. In addition, we highlight progress towards microbiota-based intervention to reduce NSAID-induced enteropathy.
非甾体抗炎药（NSAIDs）通过抑制环氧化酶同工酶（COX-1和COX-2）的活性来缓解疼痛、炎症和发热。尽管NSAIDs具有临床疗效，但它们会引起胃肠道（GI）和心血管（CV）并发症。此外，NSAIDs的使用在COX同工酶抑制程度、治疗效果和不良反应发生率方面存在显著的个体差异。肠道微生物群与宿主之间的相互作用已成为调节宿主生理、肠道微生物群相关疾病和外源性物质代谢的关键因素。事实上，宿主-肠道微生物群的动态相互作用会影响NSAIDs的处置、治疗效果和毒性。肠道微生物群可直接导致NSAIDs的化学修饰，或通过调节宿主代谢酶或过程间接影响其吸收或代谢，这可能会对药物的药代动力学和药效学性质产生影响。NSAIDs本身可直接影响肠道微生物群的组成和功能，或间接改变宿主的生理特性或功能，进而可能导致生态失调。因此，宿主-肠道微生物群与药物之间复杂的相互联系可能导致NSAIDs反应的变异性，并最终影响NSAIDs治疗的结果。在此，我们综述宿主-肠道微生物群与NSAIDs之间的相互作用及其对药物疗效和毒性的影响，主要是在胃肠道方面。此外，我们强调基于微生物群的干预措施在减少NSAIDs诱导的肠病方面取得的进展。
