Manes Annalaura, Di Renzo Tiziana, Dodani Loreta, Reale Anna, Gautiero Claudia, Di Lauro Mariastella, Nasti Gilda, Manco Federica, Muscariello Espedita, Guida Bruna, Tarantino Giovanni, Cataldi Mauro
Section of Pharmacology, Department of Neuroscience, Reproductive Sciences and Dentistry, Federico II University of Naples, 80131 Naples, Italy.
Institute of Food Sciences, National Research Council, 83100 Avellino, Italy.
Biomedicines. 2023 Sep 18;11(9):2562. doi: 10.3390/biomedicines11092562.
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
个体对传统免疫抑制剂（cIMDs）的临床反应差异很大。我们对已发表的证据进行了系统综述，以支持肠道微生物群可能通过影响cIMD的药代动力学、疗效或耐受性导致这种差异的假说。我们还综述了这些药物影响肠道微生物群组成的证据。使用特定关键词在PubMed和Scopus数据库中进行搜索，不受物种（人类或动物）或发表时间的限制。在初步数据库搜索中检索到1055篇已发表的论文。经过筛选，选择了50篇论文进行综述。在评估此问题的20篇论文中，有17篇观察到对cIMD药代动力学、疗效或耐受性的潜在影响，特别是对他克莫司、环孢素、霉酚酸和皮质类固醇，而依维莫司和西罗莫司则缺乏相关证据。在研究cIMDs对肠道微生物群影响的论文中，只有一篇报告了阴性结果，而其他所有论文均显示特定肠道细菌的相对丰度有显著变化。然而，在不同研究中未观察到微生物群修饰的独特模式。总之，现有证据支持肠道微生物群可能导致对某些cIMDs反应差异的假说，而其他药物的数据仍然缺乏。
