4-Ethylphenol

A gut-derived metabolite alters brain activity and anxiety behaviour in mice

Integration of sensory and molecular inputs from the environment shapes animal behaviour. A major site of exposure to environmental molecules is the gastrointestinal tract, in which dietary components are chemically transformed by the microbiota1 and gut-derived metabolites are disseminated to all organs, including the brain2. In mice, the gut microbiota impacts behaviour3, modulates neurotransmitter production in the gut and brain4,5, and influences brain development and myelination patterns6,7. The mechanisms that mediate the gut-brain interactions remain poorly defined, although they broadly involve humoral or neuronal connections. We previously reported that the levels of the microbial metabolite 4-ethylphenyl sulfate (4EPS) were increased in a mouse model of atypical neurodevelopment8. Here we identified biosynthetic genes from the gut microbiome that mediate the conversion of dietary tyrosine to 4-ethylphenol (4EP), and bioengineered gut bacteria to selectively produce 4EPS in mice. 4EPS entered the brain and was associated with changes in region-specific activity and functional connectivity. Gene expression signatures revealed altered oligodendrocyte function in the brain, and 4EPS impaired oligodendrocyte maturation in mice and decreased oligodendrocyte-neuron interactions in ex vivo brain cultures. Mice colonized with 4EP-producing bacteria exhibited reduced myelination of neuronal axons. Altered myelination dynamics in the brain have been associated with behavioural outcomes7,9-14. Accordingly, we observed that mice exposed to 4EPS displayed anxiety-like behaviours, and pharmacological treatments that promote oligodendrocyte differentiation prevented the behavioural effects of 4EPS. These findings reveal that a gut-derived molecule influences complex behaviours in mice through effects on oligodendrocyte function and myelin patterning in the brain.

4-Ethylphenol, 4-ethylguaiacol and 4-ethylcatechol in red wines: Microbial formation, prevention, remediation and overview of analytical approaches

The presence of 4-ethylphenol, 4-ethylguaiacol and 4-ethylcatechol in red wines affect negatively their aroma conferring horsy, barnyard, smoky and medicinal aromatic notes. These volatile phenols formed from free hydroxycinnamic acids and their ethyl esters by Dekkera/Brettanomyces yeasts, can contaminate wines. Their formation can cause serious negative economic impact to the wine industry worldwide as consumers tend to reject these wines. For these reasons various preventive and remedial treatments have been studied. This review summarises the wine microbial volatile phenols formation, preventive measures during winemaking and remedial treatments in finished wines along with their advantages and limitations for dealing with this sensory defect and impact on wine quality. Also it is important to control the levels of volatile phenols in wines using fast and convenient analytical methods namely with a detection limit below their olfactory perception threshold. The analytical methods available for quality control and performance characteristics as well their advantages and disadvantages when dealing with a complex matrix like wine are discussed in detail.

4-Ethylphenol, A Volatile Organic Compound Produced by Disease-Resistant Soybean, Is a Potential Botanical Agrochemical Against Oomycetes

Oomycetes, represented by Phytophthora, are seriously harmful to agricultural production, resulting in a decline in grain quality and agricultural products and causing great economic losses. Integrated management of oomycete diseases is becoming more challenging, and plant derivatives represent effective alternatives to synthetic chemicals as novel crop protection solutions. Biologically active secondary metabolites are rapidly synthesized and released by plants in response to biotic stress caused by herbivores or insects, as well as pathogens. In this study, we identified groups of volatile organic compounds (VOCs) from soybean plants inoculated with Phytophthora sojae, the causal agent of soybean root rot. 4-Ethylphenol was present among the identified VOCs and was induced in the incompatible interaction between the plants and the pathogen. 4-Ethylphenol inhibited the growth of P. sojae and Phytophthora nicotianae and had toxicity to sporangia formation and zoospore germination by destroying the pathogen cell membrane; it had a good control effect on soybean root rot and tobacco black shank in the safe concentration range. Furthermore, 4-Ethylphenol had a potent antifungal activity against three soil-borne phytopathogenic fungi, Rhizoctonia solani, Fusarium graminearum, and Gaeumannomyces graminis var tritici, and four forma specialis of Fusarium oxysporum, which suggest a potential to be an eco-friendly biological control agent.

4-ethylphenol and 4-ethylguaiacol in wines: estimating non-microbial sourced contributions and toxicological considerations

Analyses of commercially available wines suggested non-Brettanomyces sources of 4-ethylphenol and 4-ethylguaiacol. Grapes, enological additions, exposure to plastics, and oak-barrel aging were potential inputs considered. Investigations of whole grape bunch samples from two major red wine Vitis vinifera cultivars (L. cv. Cabernet Franc and Pinot Noir), a commercial mannoprotein additive, and three commercial enological tannin additions indicated they are not likely significant sources of these compounds. Studies on 15 commercial oak barrelled red wines from six Vitis vinifera cultivars (L. cv. Cabernet Franc, Cabernet Sauvignon, Dunkelfelder, Merlot, Pinot Meunier, and Pinot Noir), and a review of volatile phenol extraction from toasted oak wood, suggested that oak-aging may produce concentrations of up to 50 microg L(-1) 4-ethylphenol and 4-ethylguaiacol. Thus, following potential Brettanomyces-sourced aroma impacts in wine using 4-ethylphenol and/or 4-ethylguaiacol concentrations as proxies should only be considered reliable at analyte levels>100 microg L(-1). A review of worldwide 4-ethylphenol and 4-ethylguaiacol concentrations in wine, consumption patterns, and available toxicological data also suggested that levels of 4-ethylphenol being observed in wines worldwide do not warrant concerns about acute or long-term effects. While little is known about the toxicology of 4-ethylguaiacol, it is unlikely that elevated concentrations will pose any health-related concerns.

Sorption of 4-ethylphenol and 4-ethylguaiacol by suberin from cork

Cork shows an active role in the sorption of volatile phenols from wine. The sorption properties of 4-ethylphenol and 4-ethylguaiacol phenols in hydro-alcoholic medium placed in contact with suberin extracted from cork were especially investigated. To that purpose, suberin was immersed in model wine solutions containing several concentrations of each phenol and the amount of the compound remaining in the liquid phase was determined by SPME-GC-MS. Sorption isotherms of 4-ethylguaiacol and 4-ethylphenol by suberin followed the Henry's model. The solid/liquid partition coefficients (KSL) between the suberin and the model wine were also determined for several other volatile phenols. Suberin displayed rather high sorption capacity, which was positively correlated to the hydrophobicity of the volatile. Finally, the capacity of suberin to decrease the concentration of 4-ethylphenol and 4-ethylguaiacol was also tested in real wines affected by a Brettanomyces character. It also lead to a significant reduction of their concentration in wine.