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Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons

1
Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
2
Institut für Biotechnologie und Wirkstoff-Forschung gGmbH, 67663 Kaiserslautern, Germany
3
Institute for Microbiology and Wine Research, Johannes Gutenberg University Mainz, 55128 Mainz, Germany
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(15), 2776; https://doi.org/10.3390/molecules24152776
Received: 9 July 2019 / Revised: 25 July 2019 / Accepted: 26 July 2019 / Published: 30 July 2019
(This article belongs to the Section Natural Products Chemistry)
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Abstract

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 P. coprobium was identified to decrease viability with an EC50 of 0.23 ng/µL in SH-SY5Y cells and an EC50 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. View Full-Text
Keywords: enteric nervous system; fungi; fusarium; gastrointestinal system; microbiome; mycotoxins; Penicillium enteric nervous system; fungi; fusarium; gastrointestinal system; microbiome; mycotoxins; Penicillium
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Brand, B.; Stoye, N.M.; dos Santos Guilherme, M.; Nguyen, V.T.T.; Baumgaertner, J.C.; Schüffler, A.; Thines, E.; Endres, K. Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons. Molecules 2019, 24, 2776.

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