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Updated: Jan 21, 2026
An In-vitro Preparation of Isolated Enteric Neurons and Glia from the Myenteric Plexus of the Adult Mouse
Published on: August 7, 2013
Identification of Patulin from Penicillium coprobium as a Toxin for Enteric Neurons
Benjamin Brand1, Nicolai M Stoye1, Malena Dos Santos Guilherme1
1Department of Psychiatry and Psychotherapy, University Medical Center Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
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.
Insights
The fungal metabolite patulin, found in food, significantly harms human neuronal cells and primary enteric neurons by reducing viability and disrupting function. Understanding its impact is crucial for developing preventive health strategies.
Area of Science:
- Neuroscience
- Microbiology
- Toxicology
Background:
- The human gut harbors a complex fungal community (mycobiota) producing metabolites that can influence host health.
- The enteric nervous system (ENS), the gut's intrinsic neuronal network, is directly exposed to these microbial metabolites.
- Previous research has focused on bacterial gut microbiota, with less attention paid to fungal metabolites' direct impact on the ENS.
Purpose of the Study:
- To investigate the effects of fungal secondary metabolites from gut commensals on neuronal cells.
- To identify specific fungal compounds that impact neuronal viability and function.
- To assess the neurotoxic potential of identified compounds on both central nervous system (SH-SY5Y) and peripheral (enteric) neurons.
Main Methods:
- Screening of 320 fungal extracts for neurotoxic effects on human neuronal cell line (SH-SY5Y).
- Characterization of the most potent fungal extract and its active compound using spectral analysis.
- Assessing the effects of the identified compound on the viability and functionality (calcium signaling, ROS production) of primary murine enteric neurons.
Main Results:
- An extract from *P. coprobium* demonstrated significant neurotoxicity, decreasing SH-SY5Y cell viability (EC50 = 0.23 ng/µL) and enteric neuron viability (EC50 = 1 ng/µL).
- The active compound was identified as patulin, a polyketide lactone.
- Patulin induced reactive oxygen species (ROS) production in SH-SY5Y cells and caused functional impairments, including altered calcium signaling, in primary enteric neurons.
Conclusions:
- The fungal metabolite patulin exhibits direct neurotoxic effects on both central and enteric neurons.
- Patulin's ability to disrupt enteric neuron function highlights a potential mechanism for its adverse health effects, especially given its presence in food.
- Further research into patulin's impact on the ENS is warranted for developing strategies to mitigate its risks.
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