Biology, Miami University, Oxford, OH, United States.
Center for Bioinformatics and Functional Genomics, Miami University, Oxford, OH, United States.
PeerJ. 2024 Jun 3;12:e17517. doi: 10.7717/peerj.17517. eCollection 2024.
Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota.
To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition.
We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in and , and decreases in .
These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.
近年来，裸盖菇素和相关色胺类化合物作为治疗抑郁症的潜在疗法备受关注。这些作用机制的研究历史上一直集中在这些药物对神经过程的直接影响上。然而，除了这些神经作用之外，外周生理学的改变也可能有助于它们的治疗效果。特别是，大量证据支持其他药物类别的抗抑郁疗效存在肠道微生物组介导的途径，但以前没有研究确定色胺类化合物对微生物组的影响。
为了解决这一空白，在这项初步研究中，雄性长爪沙鼠用不同剂量的口服裸盖菇素（0.2 或 2mg/kg）、norbaeocystin（0.25 或 2.52mg/kg）或载体处理，并在暴露后 1 周和 3 周收集粪便样本，用于微生物组分析，使用整合的 16S 核糖体 DNA 测序来确定肠道微生物组组成。
我们发现，尽管裸盖菇素和 norbaeocystin 的治疗都没有显著影响微生物组的整体多样性，但它确实导致了门水平细菌丰度的显著剂量和时间依赖性变化，包括增加和减少。
这些初步发现支持了裸盖菇素和其他色胺类化合物可能以剂量和时间依赖的方式作用于肠道微生物组的观点，这可能为它们的抗抑郁活性提供了一种新的外周机制。这项初步研究的结果还表明，norbaeocystin 可能值得进一步研究，作为一种潜在的抗抑郁药，因为它的作用与裸盖菇素相似。
