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Updated: May 7, 2026
Studying Neurobehavioral Effects of Environmental Pollutants on Zebrafish Larvae
Published on: February 5, 2020
Methylparaben Induces Gut Microbiota-Dependent Neurotoxicity in Zebrafish
Jiazhen Wang1,2, Jingchuan Xue3,4,5, Yiling Lin3,4,5
1Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China.
Abstract:
The neurotoxic effects of parabens have been previously proposed, however, the mechanisms driving its neurotoxicity remain largely uncharacterized. To better understand and identify the underlying mechanistic effects, methylparaben (MeP), the most common paraben produced, was exposed to embryonic zebrafish (Danio rerio) at environmentally relevant concentrations. Nontargeted and targeted metabolomics revealed that MeP primarily disrupted neurotransmitter-related metabolic pathways, leading to altered levels of gut microbiota associated neuroactive metabolites, suggesting impairment of neurobehavioral regulatory functions. Concurrently, MeP exposure significantly reduced locomotor activity, providing behavioral evidence for its neurotoxic effects. Comparisons between germ-free and conventionally reared zebrafish demonstrated that the absence of gut microbiota markedly alleviated MeP-induced neurotoxicity, as evidenced by weaker perturbations in neurotransmitter profiles and swimming behavior. Further, stable isotope-assisted high-resolution mass spectrometry revealed that gut microbes could reverse phase II detoxification through deconjugation reactions, regenerating MeP and enhancing systemic exposure. Overall, this study first reveals that MeP induces neurotoxicity through gut microbiota-mediated metabolic remodeling and biotransformation, providing new insights into the ecological risks of parabens.
Insights
Methylparaben (MeP) causes neurotoxicity by altering gut microbe metabolism and biotransformation. The absence of gut microbiota significantly reduces MeP-induced neurotoxic effects in zebrafish.
Area of Science:
- Environmental toxicology
- Neuroscience
- Microbiome research
Background:
- Parabens are widely used preservatives with proposed neurotoxic effects.
- The mechanisms underlying paraben neurotoxicity are not well understood.
- Methylparaben (MeP) is the most prevalent paraben, necessitating investigation into its biological impacts.
Purpose of the Study:
- To elucidate the mechanisms of methylparaben (MeP)-induced neurotoxicity.
- To investigate the role of gut microbiota in MeP neurotoxicity.
- To assess the ecological risks associated with paraben exposure.
Main Methods:
- Exposure of embryonic zebrafish (Danio rerio) to environmentally relevant concentrations of MeP.
- Utilized nontargeted and targeted metabolomics to analyze metabolic disruptions.
- Employed stable isotope-assisted high-resolution mass spectrometry for biotransformation analysis.
- Compared neurotoxicity in germ-free versus conventionally reared zebrafish.
Main Results:
- MeP disrupted neurotransmitter metabolism and altered neuroactive metabolites produced by gut microbiota.
- MeP exposure significantly reduced locomotor activity in zebrafish.
- The absence of gut microbiota alleviated MeP-induced neurotoxicity and behavioral deficits.
- Gut microbes were found to regenerate MeP through deconjugation, increasing systemic exposure.
Conclusions:
- MeP induces neurotoxicity primarily through gut microbiota-mediated metabolic remodeling and biotransformation.
- Gut microbiota play a critical role in modulating MeP's neurotoxic effects.
- This study highlights the ecological risks of parabens and their interaction with the gut microbiome.
