Department of Medicine, Division of Rheumatology, New York University Langone Health, New York, NY, USA.
Rheumatology Division, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Nat Rev Rheumatol. 2020 May;16(5):282-292. doi: 10.1038/s41584-020-0395-3. Epub 2020 Mar 10.
In the past three decades, extraordinary advances have been made in the understanding of the pathogenesis of, and treatment options for, inflammatory arthritides, including rheumatoid arthritis and spondyloarthritis. The use of methotrexate and subsequently biologic therapies (such as TNF inhibitors, among others) and oral small molecules have substantially improved clinical outcomes for many patients with inflammatory arthritis; for others, however, these agents do not substantially improve their symptoms. The emerging field of pharmacomicrobiomics, which investigates the effect of variations within the human gut microbiome on drugs, has already provided important insights into these therapeutics. Pharmacomicrobiomic studies have demonstrated that human gut microorganisms and their enzymatic products can affect the bioavailability, clinical efficacy and toxicity of a wide array of drugs through direct and indirect mechanisms. This discipline promises to facilitate the advent of microbiome-based precision medicine approaches in inflammatory arthritis, including strategies for predicting response to treatment and for modulating the microbiome to improve response to therapy or reduce drug toxicity.
在过去的三十年中,人们对炎症性关节炎(包括类风湿关节炎和脊柱关节炎)的发病机制和治疗选择有了非凡的认识。甲氨蝶呤的应用以及随后的生物疗法(如 TNF 抑制剂等)和口服小分子药物极大地改善了许多炎症性关节炎患者的临床结局;然而,对于其他人来说,这些药物并没有显著改善他们的症状。药物微生物组学这一新兴领域研究了人类肠道微生物组内的变异对药物的影响,它已经为这些治疗方法提供了重要的见解。药物微生物组学研究表明,人类肠道微生物及其酶产物可以通过直接和间接机制影响多种药物的生物利用度、临床疗效和毒性。这一学科有望促进炎症性关节炎基于微生物组的精准医学方法的出现,包括预测治疗反应的策略,以及调节微生物组以改善治疗反应或降低药物毒性的策略。