{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:27:57Z","timestamp":1785414477812,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["FIS\/IMSS\/R-2021-785-057"],"award-info":[{"award-number":["FIS\/IMSS\/R-2021-785-057"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"award":["FIS\/IMSS\/R-2021-785-057"],"award-info":[{"award-number":["FIS\/IMSS\/R-2021-785-057"]}],"id":[{"id":"https:\/\/ror.org\/03xddgg98","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005739","name":"DGAPA, Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico","doi-asserted-by":"publisher","award":["IN210024"],"award-info":[{"award-number":["IN210024"]}],"id":[{"id":"10.13039\/501100005739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["CNS2022-136008"],"award-info":[{"award-number":["CNS2022-136008"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011011","name":"Junta de Andaluc\u00eda","doi-asserted-by":"crossref","award":["30318"],"award-info":[{"award-number":["30318"]}],"id":[{"id":"10.13039\/501100011011","id-type":"DOI","asserted-by":"crossref"}]},{"award":["30318"],"award-info":[{"award-number":["30318"]}],"id":[{"id":"https:\/\/ror.org\/01jem9c82","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Karolinska Institutet Forskningsstiftelser\/KI Research","award":["2024-02763"],"award-info":[{"award-number":["2024-02763"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The gut microbiota produces molecules that trigger responses at the local and distant levels. It affects the brain through several metabolic products, including serotonin (5-HT). Tryptophan hydroxylase type 1 (Tph1) is the rate-limiting enzyme during 5-HT biosynthesis in the gut. Efavirenz (EFV), an antiretroviral agent against HIV, is associated with depression disorders and Tryptophan hydroxylase type 2 (Tph2) deregulation in mice. The possible association between the depressive effects of EFV secondary to dysbiosis and the expression of Tph1 in the intestine is yet to be studied. Therefore, we aimed to elucidate the role of the gut microbiota in depression mechanisms. We reviewed the gut microbiota, their metabolites (short-chain fatty acids [SCFA]), Tph1 expression in the gut, and systemic 5-HT and tryptophan levels in CD1 mice after 36 days of oral EFV (10 mg\/kg) treatment. The proportions of Bacteroidota and Bacillota_A_368345 decreased and increased, respectively, following EFV treatment. Additionally, the abundance of Lactobacillus spp. and Faecalbaculum decreased, whereas that of Dubosiella spp., Blautia_A_141780, and Anaerostipes increased. These bacteria contribute to SCFA production and may have counteracted the lack of protective effects provided by Lactobacillus. Tph1 expression was dysregulated in the gut, whereas serum 5-HT levels decreased following EFV treatment. Lactobacillus species promote 5-HT production in the gut, and the deregulation of Tph1 affects 5-HT synthesis. This disruption in the gut\u2013brain axis decreased peripheral 5-HT levels. This affects the serotonergic system in the brain, which could contribute to depression.<\/jats:p>","DOI":"10.3390\/ijms27104504","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efavirenz-Altered Gut-Microbiota, Tph1, and Systemic 5-HT Levels: Could They Affect Depression Mechanisms in Mice?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1525-8496","authenticated-orcid":false,"given":"Sandra Ang\u00e9lica","family":"Rojas-Osornio","sequence":"first","affiliation":[{"name":"Academia de Bioqu\u00edmica M\u00e9dica II, Departamento de Formaci\u00f3n B\u00e1sica Disciplinaria, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5327-1643","authenticated-orcid":false,"given":"Vladimir","family":"Paredes-Cervantes","sequence":"additional","affiliation":[{"name":"Laboratorio Central, Hospital de Especialidades \u201cDr. Antonio Fraga Mouret\u201d, Centro M\u00e9dico Nacional \u201cLaRaza\u201d, Instituto Mexicano del Seguro Social, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-9995","authenticated-orcid":false,"given":"Mar\u00eda Magdalena","family":"Aguirre-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unidad de Investigacio\u0301n UNAM-INC, Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Universidad Nacional Auto\u0301noma de Me\u0301xico, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minerva","family":"Crespo-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Division de Neurociencias, Instituto de Fisiolog\u00eda Celular, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4311-381X","authenticated-orcid":false,"given":"Claudia C.","family":"M\u00e1rquez-Mota","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n Animal y Bioqu\u00edmica, Facultad de Medicina Veterinaria y Zoot\u00e9cnia, Universidad Nacional Auto\u0301noma de Me\u0301xico, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8236-2986","authenticated-orcid":false,"given":"Raquel","family":"Aguilar-Rosales","sequence":"additional","affiliation":[{"name":"Unidad de Investigacio\u0301n UNAM-INC, Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Universidad Nacional Auto\u0301noma de Me\u0301xico, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mois\u00e9s","family":"Talamantes-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Departamento de Nutrici\u00f3n Animal y Bioqu\u00edmica, Facultad de Medicina Veterinaria y Zoot\u00e9cnia, Universidad Nacional Auto\u0301noma de Me\u0301xico, Mexico City 02990, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-2939","authenticated-orcid":false,"given":"Alma Reyna","family":"Escalona-Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Unidad de Investigacio\u0301n UNAM-INC, Divisi\u00f3n de Investigaci\u00f3n, Facultad de Medicina, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Universidad Nacional Auto\u0301noma de 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Asp. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.bbi.2023.11.016","article-title":"Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis","volume":"115","author":"Zheng","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3560","DOI":"10.3748\/wjg.v30.i30.3560","article-title":"Link between childhood obesity and gut microbiota","volume":"30","author":"Pan","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vamanu, E., and Rai, S.N. (2021). The Link between Obesity, Microbiota Dysbiosis, and Neurodegenerative Pathogenesis. Diseases, 9.","DOI":"10.3390\/diseases9030045"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41423-025-01263-0","article-title":"Gut-derived macrophages link intestinal damage to brain injury after cardiac arrest through TREM1 signaling","volume":"22","author":"Chang","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e14193","DOI":"10.1111\/apha.14193","article-title":"The gut-immune axis during hypertension and cardiovascular diseases","volume":"240","author":"Dinakis","year":"2024","journal-title":"Acta Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1097\/HCO.0000000000000445","article-title":"Gut microbiome and its role in cardiovascular diseases","volume":"32","author":"Ahmadmehrabi","year":"2017","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/15622975.2025.2530750","article-title":"Assessing the relationship of gut microbiota with neurological, psychiatric, and neurodegenerative disorders: A narrative review","volume":"26","author":"Batagianni","year":"2025","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4879","DOI":"10.1007\/s00210-025-04776-7","article-title":"The gut-brain axis: Role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics","volume":"399","author":"Aijaz","year":"2026","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40168-016-0222-x","article-title":"Gut microbiota dysbiosis contributes to the development of hypertension","volume":"5","author":"Li","year":"2017","journal-title":"Microbiome"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"111140","DOI":"10.1016\/j.cellsig.2024.111140","article-title":"Exploration of gut microbiome and inflammation: A review on key signalling pathways","volume":"118","author":"Nigam","year":"2024","journal-title":"Cell Signal."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Al Bander, Z., Nitert, M.D., Mousa, A., and Naderpoor, N. (2020). The Gut Microbiota and Inflammation: An Overview. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17207618"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.47892\/rgp.2022.422.1438","article-title":"Eje cerebro intestino microbiota. Importancia en la pr\u00e1ctica cl\u00ednica","volume":"42","author":"Hanna","year":"2022","journal-title":"Rev. Gastroenterol. Per\u00fa"},{"key":"ref_14","unstructured":"Recker, J. (Smithsonian Magazine, 2019). Scientists Find a Possible Link Between Gut Bacteria and Depression, Smithsonian Magazine."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"176014","DOI":"10.1016\/j.ejphar.2023.176014","article-title":"Implication of microbiota gut-brain axis in the manifestation of obsessive-compulsive disorder: Preclinical and clinical evidence","volume":"957","author":"Kamble","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7129","DOI":"10.1038\/s41467-022-34504-1","article-title":"The gut microbiota and depressive symptoms across ethnic groups","volume":"13","author":"Bosch","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jnutbio.2019.01.007","article-title":"Bifidobacterium with the role of 5-hydroxytryptophan synthesis regulation alleviates the symptom of depression and related microbiota dysbiosis","volume":"66","author":"Tian","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/jnc.14709","article-title":"Increasing carbohydrate availability in the hindgut promotes hypothalamic neurotransmitter synthesis: Aromatic amino acids linking the microbiota-brain axis","volume":"149","author":"Gao","year":"2019","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/jnc.14333","article-title":"Antibiotics-induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets","volume":"146","author":"Gao","year":"2018","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13416","article-title":"Recent developments in understanding the role of the gut microbiota in brain health and disease","volume":"1420","author":"Sherwin","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/nm.4106","article-title":"Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor","volume":"22","author":"Rothhammer","year":"2016","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/hiv.12104","article-title":"Risk of clinically significant depression in HIV infected patients: Effect of antiretroviral drugs","volume":"15","author":"Padilla","year":"2014","journal-title":"HIV Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.3727\/096368916X691457","article-title":"HIV Non-Nucleoside Reverse Transcriptase Inhibitor Efavirenz Reduces Neural Stem Cell Proliferation in Vitro and in Vivo","volume":"25","author":"Jin","year":"2016","journal-title":"Cell Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/tmi.13021","article-title":"Efavirenz is related to neuropsychiatric symptoms among adults, but not among adolescents livin with human immunodeficiency virus in Kilimanjaro, Tanzania","volume":"23","author":"Schellekens","year":"2018","journal-title":"Trop. Med. Int. Health"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s11064-011-0432-3","article-title":"Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine inhibit cytochrome C oxidase in mouse brain regions","volume":"36","author":"Streck","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1007\/s12035-018-1273-8","article-title":"Nanoformulated Antiretroviral Therapy Attenuates Brain Metabolic Oxidative Stress","volume":"56","author":"Woldstad","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1124\/pr.117.013706","article-title":"Adverse Neuropsychiatric Events and Recreational Use of Efavirenz and Other HIV-1 Antiretroviral Drugs","volume":"70","author":"Dalwadi","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1118580","DOI":"10.3389\/fphar.2023.1118580","article-title":"Antiretroviral drugs efavirenz, dolutegravir and bictegravir dysregulate blood-brain barrier integrity and function","volume":"14","author":"Huang","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Rojas-Osornio, S.A., Crespo-Ram\u00edrez, M., Paredes-Cervantes, V., Mata-Mar\u00edn, A., Mart\u00ednez-Lara, R., P\u00e9rez de la Mora, M., and Tesoro-Cruz, E. (2024). Oral Administration of Efavirenz Dysregulates the Tph2 Gene in Brain Serotonergic Areas and Alters Weight and Mood in Mice. Pharmaceuticals, 801.","DOI":"10.3390\/ph17060801"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1021\/acsinfecdis.0c00536","article-title":"Altered Gut Microbiome under Antiretroviral Therapy: Impact of Efavirenz and Zidovudine","volume":"7","author":"Ray","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23099","DOI":"10.1021\/acsomega.5c01210","article-title":"Comparison of Efavirenz and Dolutegravir on Gut Microbiome and Gut Barrier Functions","volume":"10","author":"Huang","year":"2025","journal-title":"ACS Omega"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e21648","DOI":"10.1096\/fj.202100366R","article-title":"Phenylalanine hydroxylase contributes to serotonin synthesis in mice","volume":"35","author":"Mordhorst","year":"2021","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/jnc.12779","article-title":"Functional characterization of the S41Y (C2755A) polymorphism of tryptophan hydroxylase 2","volume":"130","author":"Salli","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.brainresbull.2011.01.006","article-title":"TPH2 in the ventral tegmental area of the male rat brain","volume":"84","author":"Salli","year":"2011","journal-title":"Brain Res. Bull."},{"key":"ref_35","first-page":"10729","article-title":"Efavirenz as a psychotropic drug","volume":"24","author":"Zareifopoulos","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1093\/infdis\/jiu825","article-title":"Involvement of nitric oxide in the mitochondrial action of efavirenz: A differential effect on neurons and glial cells","volume":"21","author":"Apostolova","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ejphar.2017.02.009","article-title":"HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: Evaluation of neurotransmitter alterations in the striatum","volume":"799","author":"Cavalcante","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1124\/dmd.119.086348","article-title":"Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry","volume":"47","author":"Wang","year":"2019","journal-title":"Drug Metab. Dispos."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114985","DOI":"10.1016\/j.biopha.2023.114985","article-title":"Immunological mechanisms of inflammatory diseases caused by gut microbiota dysbiosis: A review","volume":"164","author":"Zhao","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"158","DOI":"10.5607\/en.2019.28.2.158","article-title":"Extracellular Vesicles Derived from Lactobacillus plantarum Increase BDNF Expression in Cultured Hippocampal Neurons and Produce Antidepressant-like Effects in Mice","volume":"28","author":"Choi","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Skowro\u0144ska, A., Gawlik-Kotelnicka, O., Margulska, A., and Strzelecki, D. (2023). The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms; Function and Composition of Gut Microbiota; and Metabolic, Inflammation, and Oxidative Stress Markers in Patients with Depression-A Study Protocol. Metabolites, 13.","DOI":"10.3390\/metabo13020182"},{"key":"ref_42","first-page":"501","article-title":"Probiotics, gut microbiota, and brain health: Exploring therapeutic pathways","volume":"11","author":"Vijayaram","year":"2025","journal-title":"AIMS Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Knezevic, E., Nenic, K., Milanovic, V., and Knezevic, N.N. (2023). The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells, 12.","DOI":"10.3390\/cells12232726"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e70168","DOI":"10.1002\/mco2.70168","article-title":"Gut Microbiota Dysbiosis: Pathogenesis, Diseases, Prevention, and Therapy","volume":"6","author":"Shen","year":"2025","journal-title":"MedComm"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"150218","DOI":"10.1016\/j.bbrc.2024.150218","article-title":"GABAergic implications in anxiety and related disorders","volume":"724","author":"Arora","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.chembiol.2015.02.005","article-title":"Biosynthetic manipulation of tryptophan in bacteria: Pathways and mechanisms","volume":"22","author":"Alkhalaf","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112680","DOI":"10.1016\/j.nut.2024.112680","article-title":"Probiotics and undernourishment impact on brain 5-Hydroxytryptamine system and neurotrophin BDNF in rats: Risk of depression and anxiety?","volume":"132","author":"Alves","year":"2025","journal-title":"Nutrition"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41564-019-0649-5","article-title":"Endogenous murine microbiota member Faecalibaculum rodentium and its human homologue protect from intestinal tumour growth","volume":"5","author":"Zagato","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rojas-Osornio, S.A., Manuel-Apolinar, L., Crespo-Ram\u00edrez, M., Paredes-Cervantes, V., Mata-Mar\u00edn, A., Molina-L\u00f3pez, J., P\u00e9rez de la Mora, M., Borroto-Escuela, D., Mart\u00ednez-Lara, R., and Tesoro-Cruz, E. (2026). Efavirenz Interacts with Hormones Involved in Appetite and Satiety, Affecting Body Weight in Mice. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27020735"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"111572","DOI":"10.1016\/j.mce.2022.111572","article-title":"Short chain fatty acids: Microbial metabolites for gut-brain axis signalling","volume":"546","author":"Collins","year":"2022","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fusco, W., Lorenzo, M.B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M.C., Gasbarrini, A., and Collado, M.C. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15092211"},{"key":"ref_52","unstructured":"Chapp, A.D., Shan, Z., and Chen, Q.H. (2024). \u00c1cido ac\u00e9tico: Un metabolito subestimado en los cambios inducidos por el etanol en la regulaci\u00f3n de la funci\u00f3n cardiovascular. Antioxidantes, 13."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"102732","DOI":"10.1016\/j.micron.2019.102732","article-title":"Effect of propionic acid on the morphology of the amygdala in adolescent male rats and their behavior","volume":"125","author":"Lobzhanidze","year":"2019","journal-title":"Micron"},{"key":"ref_54","first-page":"1","article-title":"Use of microbial fuel cell systems in wastewater treatment in connection with bioenergy generation","volume":"12","author":"Aires","year":"2025","journal-title":"Rev. Desafios"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"157381","DOI":"10.1016\/j.phymed.2025.157381","article-title":"6-shogaol improves the cognitive and memory declines of natural aging mice by modulating butyrate-producing microbiota and intestinal barrier","volume":"148","author":"Zhu","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cao, J., Ma, J., Zha, X., Bian, X., Wang, W., and Liu, X. (2026). Gut Microbiota Dysbiosis in Depression: Pathological Correlations, Molecular Pathways, and Therapeutic Interventions. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27031530"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1097\/HJH.0000000000004254","article-title":"Prospective association between the gut microbiome and incident hypertension: A 20-year cohort study","volume":"44","author":"Yeo","year":"2026","journal-title":"J. Hypertens."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e0081623","DOI":"10.1128\/msphere.00816-23","article-title":"Anaerostipes hadrus, a butyrate-producing bacterium capable of metabolizing 5-fluorouracil","volume":"9","author":"Liu","year":"2024","journal-title":"mSphere"},{"key":"ref_59","first-page":"102510","article-title":"Anaerostipes caccae CLB101TM, a Novel Probiotic and Key Butyrate Producer, Aids in the Resolution of Long-Term Food Intolerances in a Patient in 12 Weeks: A Case Report","volume":"11","author":"Coetzee","year":"2026","journal-title":"Ann. Case Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"101760","DOI":"10.1016\/j.xcrm.2024.101760","article-title":"The penetration of therapeutics across the blood-brain barrier: Classic case studies and clinical implications","volume":"5","author":"Banks","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2020.1869501","article-title":"Involvement of the microbiota-gut-brain axis in chronic restraint stress: Disturbances of the kynurenine metabolic pathway in both the gut and brain","volume":"13","author":"Deng","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_62","unstructured":"(1999). Norma Oficial Mexicana Para la Producci\u00f3n, Cuidado y Uso de los Animales de Laboratorio; Chapter 9 (Standard No. NOM-062-Z00-1999)."},{"key":"ref_63","unstructured":"Fletcher, C., and Crossgrove, R. (2026, February 10). Guide for the Care and Use of Laboratory Animals, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK54050\/."},{"key":"ref_64","unstructured":"(2026, February 10). NC3Rs. National Centre for the Replacement, Refinement and Reduction of Animals in Research. ARRIVE Guidelines. Available online: https:\/\/arriveguidelines.org\/."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s12640-009-9141-y","article-title":"Anti-HIV drugs nevirapine and efavirenz affect anxiety-related behavior and cognitive performance in mice","volume":"19","author":"Lemos","year":"2011","journal-title":"Neurotox. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s11011-008-9109-2","article-title":"Effects of the HIV treatment drugs nevirapine and efavirenz on brain creatine kinase activity","volume":"23","author":"Streck","year":"2008","journal-title":"Metab. Brain Dis."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Magzal, F., Even, C., Haimov, I., Agmon, M., Asraf, K., Shochat, T., and Tami, S. (2021). Associations between fecal short-chain fatty acids and sleep continuity in older adults with insomnia symptoms. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-83389-5"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4504\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:29:23Z","timestamp":1779251363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":67,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104504"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104504","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}