Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Institut für Biotechnologie und Wirkstoff-Forschung gGmbH, 67663 Kaiserslautern, Germany.
Molecules. 2019 Jul 30;24(15):2776. doi: 10.3390/molecules24152776.
The identification and characterization of fungal commensals of the human gut (the mycobiota) is ongoing, and the effects of their various secondary metabolites on the health and disease of the host is a matter of current research. While the neurons of the central nervous system might be affected indirectly by compounds from gut microorganisms, the largest peripheral neuronal network (the enteric nervous system) is located within the gut and is exposed directly to such metabolites. We analyzed 320 fungal extracts and their effect on the viability of a human neuronal cell line (SH-SY5Y), as well as their effects on the viability and functionality of the most effective compound on primary enteric neurons of murine origin. An extract from was identified to decrease viability with an EC of 0.23 ng/µL in SH-SY5Y cells and an EC of 1 ng/µL in enteric neurons. Further spectral analysis revealed that the effective compound was patulin, and that this polyketide lactone is not only capable of evoking ROS production in SH-SY5Y cells, but also diverse functional disabilities in primary enteric neurons such as altered calcium signaling. As patulin can be found as a common contaminant on fruit and vegetables and causes intestinal injury, deciphering its specific impact on enteric neurons might help in the elaboration of preventive strategies.
人类肠道共生真菌（真菌群落）的鉴定和特征正在进行中，其各种次级代谢产物对宿主健康和疾病的影响是当前研究的一个课题。虽然中枢神经系统的神经元可能会受到肠道微生物化合物的间接影响，但最大的外周神经元网络（肠神经系统）位于肠道内，直接暴露于这些代谢物中。我们分析了 320 种真菌提取物及其对人神经母细胞瘤细胞系（SH-SY5Y）活力的影响，以及对最有效化合物对源自鼠的原代肠神经元活力和功能的影响。从 中鉴定出一种提取物，其在 SH-SY5Y 细胞中的 EC50 为 0.23ng/µL，在肠神经元中的 EC50 为 1ng/µL，可降低活力。进一步的光谱分析表明，有效化合物是棒曲霉素，这种聚酮内酯不仅能够在 SH-SY5Y 细胞中引发 ROS 产生，还能够导致原代肠神经元产生多种功能障碍，如钙信号改变。由于棒曲霉素可以作为水果和蔬菜的常见污染物存在，并导致肠道损伤，因此阐明其对肠神经元的具体影响可能有助于制定预防策略。
