Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Dept. of Medicine and Surgery, University of Milano - Bicocca, Milan, Italy.
Psychoneuroendocrinology. 2022 Sep;143:105828. doi: 10.1016/j.psyneuen.2022.105828. Epub 2022 Jun 9.
Paroxetine, a selective serotonin reuptake inhibitor (SSRI), is prescribed to treat psychiatric disorders, although an off-label SSRI use is also for functional gastrointestinal disorders. The mutual correlation between serotonin and peripheral sex steroids has been reported, however little attention to sex steroids synthesized by gut, has been given so far. Indeed, whether SSRIs, may also influence the gut steroid production, immediately after treatment and/or after suspension, is still unclear. The finding that gut possesses steroidogenic capability is of particular relevance, also for the existence of the gut-microbiota-brain axis, where gut microbiota represents a key orchestrator. On this basis, adult male rats were treated daily for two weeks with paroxetine or vehicle and, 24 h after treatment and at 1 month of withdrawal, steroid environment and gut microbiota were evaluated. Results obtained reveal that paroxetine significantly affects steroid levels, only in the colon but not in plasma. In particular, steroid modifications observed immediately after treatment are not overlap with those detected at withdrawal. Additionally, paroxetine treatment and its withdrawal impact gut microbiota populations differently. Altogether, these results suggest a biphasic effect of the drug treatment in the gut both on steroidogenesis and microbiota.
帕罗西汀是一种选择性 5-羟色胺再摄取抑制剂（SSRI），用于治疗精神疾病，但也有非标签适应证，用于治疗功能性胃肠疾病。已经报道了 5-羟色胺与外周性激素之间的相互关联，但迄今为止，对肠道合成的性激素关注甚少。事实上，SSRI 是否也会影响肠道类固醇的产生，无论是在治疗后立即还是停药后，目前尚不清楚。肠道具有类固醇生成能力的发现尤其重要，这也与肠道微生物群-大脑轴的存在有关，其中肠道微生物群是关键的协调器。在此基础上，成年雄性大鼠连续两周每天用帕罗西汀或载体处理，在治疗后 24 小时和停药 1 个月时，评估类固醇环境和肠道微生物群。结果表明，帕罗西汀仅在结肠中，而不在血浆中显著影响类固醇水平。特别是，治疗后立即观察到的类固醇变化与停药时检测到的变化并不重叠。此外，帕罗西汀治疗及其停药对肠道微生物群的影响不同。总之，这些结果表明，药物治疗在肠道中对类固醇生成和微生物群有双相作用。
