Publications

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

  Needham B.D., Funabashi M., Adame M.D., Wang Z., Boktor J.C., Haney J., Wu W.L., Rabut C., Ladinsky M.S., Hwang S.J., Guo Y., Zhu Q., Griffiths J.A., Knight R., Bjorkman P.J., Shapiro M.G., Geschwind D.H., Holschneider D.P., Fischbach M.A., Mazmanian S.K.

  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 dissemin ... >> More

  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 brain^4,5, and influences brain development and myelination patterns^6,7. 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 outcomes^7,9-14. 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. << Less

  Nature 602:647-653(2022) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Ethylphenol Formation by Lactobacillus plantarum: Identification of the Enzyme Involved in the Reduction of Vinylphenols.

  Santamaria L., Reveron I., de Felipe F.L., de Las Rivas B., Munoz R.

  Ethylphenols are strong odorants produced by microbial activity that are described as off flavors in several foods. <i>Lactobacillus plantarum</i> is a lactic acid bacterial species able to produce ethylphenols by the reduction of vinylphenols during the metabolism of hydroxycinnamic acids. Howeve ... >> More

  Ethylphenols are strong odorants produced by microbial activity that are described as off flavors in several foods. <i>Lactobacillus plantarum</i> is a lactic acid bacterial species able to produce ethylphenols by the reduction of vinylphenols during the metabolism of hydroxycinnamic acids. However, the reductase involved has not been yet uncovered. In this study, the involvement in vinylphenol reduction of a gene encoding a putative reductase (<i>lp_3125</i>) was confirmed by the absence of reduction activity in the Δ<i>lp_3125</i> knockout mutant. The protein encoded by <i>lp_3125</i>, VprA, was recombinantly produced in <i>Escherichia coli</i> VprA was assayed against vinylphenols (4-vinylphenol, 4-vinylcatechol, and 4-vinylguaiacol), and all were reduced to their corresponding ethylphenols (4-ethylphenol, 4-ethylcatechol, and 4-ethylguaiacol). PCR and high-performance liquid chromatography (HPLC) detection methods revealed that the VprA reductase is not widely distributed among the lactic acid bacteria studied and that only the bacteria possessing the <i>vprA</i> gene were able to produce ethylphenol from vinylphenol. However, all the species belonging to the <i>L. plantarum</i> group were ethylphenol producers. The identification of the <i>L. plantarum</i> VprA protein involved in hydroxycinnamate degradation completes the route of degradation of these compounds in lactic acid bacteria.<b>IMPORTANCE</b> The presence of volatile phenols is considered a major organoleptic defect of several fermented alcoholic beverages. The biosynthesis of these compounds has been mainly associated with <i>Brettanomyces</i>/<i>Dekkera</i> yeasts. However, the potential importance of lactic acid bacteria in volatile phenol spoilage is emphasized by reports describing a faster ethylphenol production by these bacteria than by yeasts. The genetic identification of the bacterial vinylphenol reductase involved in volatile phenol production provides new insights into the role of lactic acid bacteria in the production of these off flavors. The development of a molecular method for the detection of ethylphenol-producing bacteria could be helpful to design strategies to reduce the bacterial production of vinylphenols in fermented foods. << Less

  Appl. Environ. Microbiol. 84:e01064-e01064(2018) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.