Changes in brain kynurenine levels via gut microbiota and gut‐barrier disruption induced by chronic ethanol exposure in mice
| العنوان: | Changes in brain kynurenine levels via gut microbiota and gut‐barrier disruption induced by chronic ethanol exposure in mice |
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| المؤلفون: | Luis Alou Cervera, María Isabel Colado, Esther O'Shea, Pablo Giménez-Gómez, David Martín-Hernández, María Luisa Gómez-Lus Centelles, María Dolores Gutiérrez-López, Mercedes Pérez-Hernández, Javier R. Caso |
| المصدر: | FASEB J |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Inflammation, Gut flora, Matrix metalloproteinase, digestive system, Biochemistry, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Genetics, medicine, Animals, Molecular Biology, Kynurenine, Ethanol, Behavior, Animal, biology, Gut barrier, Research, Tryptophan, Brain, Metabolism, biology.organism_classification, Gastrointestinal Microbiome, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, chemistry, medicine.symptom, 030217 neurology & neurosurgery, Biotechnology |
| الوصف: | Inflammatory processes have been shown to modify tryptophan (Trp) metabolism. Gut microbiota appears to play a significant role in the induction of peripheral and central inflammation. Ethanol (EtOH) exposure alters gut permeability, but its effects on Trp metabolism and the involvement of gut microbiota have not been studied. We analyzed several parameters of gut-barrier and of peripheral and central Trp metabolism following 2 different EtOH consumption patterns in mice, the binge model, drinking in the dark (DID), and the chronic intermittent (CI) consumption paradigm. Antibiotic treatment was used to evaluate gut microbiota involvement in the CI model. Mice exposed to CI EtOH intake, but not DID, show bacterial translocation and increased plasma LPS immediately after EtOH removal. Gut-barrier permeability to FITC-dextran is increased by CI, and, furthermore, intestinal epithelial tight-junction (TJ) disruption is observed (decreased expression of zonula occludens 1 and occludin) associated with increased matrix metalloproteinase (MMP)-9 activity and iNOS expression. CI EtOH, but not DID, increases kynurenine (Kyn) levels in plasma and limbic forebrain. Intestinal bacterial decontamination prevents the LPS increase but not the permeability to FITC-dextran, TJ disruption, or the increase in MMP-9 activity and iNOS expression. Although plasma Kyn levels are not affected by antibiotic treatment, the elevation of Kyn in brain is prevented, pointing to an involvement of microbiota in CI EtOH–induced changes in brain Trp metabolism. Additionally, CI EtOH produces depressive-like symptoms of anhedonia, which are prevented by the antibiotic treatment thus pointing to an association between anhedonia and the increase in brain Kyn and to the involvement of gut microbiota.—Giménez-Gómez, P., Pérez-Hernández, M., O’Shea, E., Caso, J. R., Martín-Hernández, D., Cervera, L. A., Centelles. M. L. G.-L., Gutiérrez-Lopez, M. D., Colado, M. I. Changes in brain kynurenine levels via gut microbiota and gut-barrier disruption induced by chronic ethanol exposure in mice. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da98021475aad6b8968a77e388a89f5b https://doi.org/10.1096/fj.201900491rr |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....da98021475aad6b8968a77e388a89f5b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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