{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:52:10Z","timestamp":1792252330571,"version":"4.4.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,15]],"date-time":"2023-04-15T00:00:00Z","timestamp":1681516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","doi-asserted-by":"publisher","award":["543626-19"],"award-info":[{"award-number":["543626-19"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","doi-asserted-by":"publisher","award":["IT13530"],"award-info":[{"award-number":["IT13530"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"MITACS","doi-asserted-by":"publisher","award":["543626-19"],"award-info":[{"award-number":["543626-19"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004489","name":"MITACS","doi-asserted-by":"publisher","award":["IT13530"],"award-info":[{"award-number":["IT13530"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nutrition and Mental Health Master\u2019s Scholarship, University of Ottawa","award":["543626-19"],"award-info":[{"award-number":["543626-19"]}]},{"name":"Nutrition and Mental Health Master\u2019s Scholarship, University of Ottawa","award":["IT13530"],"award-info":[{"award-number":["IT13530"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis.<\/jats:p>","DOI":"10.3390\/ijms24087326","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T03:14:09Z","timestamp":1681701249000},"page":"7326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5235-5474","authenticated-orcid":false,"given":"Yasmina","family":"Ait Chait","sequence":"first","affiliation":[{"name":"NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1260-2140","authenticated-orcid":false,"given":"Walid","family":"Mottawea","sequence":"additional","affiliation":[{"name":"NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-2265","authenticated-orcid":false,"given":"Thomas A.","family":"Tompkins","sequence":"additional","affiliation":[{"name":"Lallemand Bio-Ingredients, Montreal, QC H1W 2N8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-5639","authenticated-orcid":false,"given":"Riadh","family":"Hammami","sequence":"additional","affiliation":[{"name":"NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-Altering Microorganisms: The Impact of the Gut Microbiota on Brain and Behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbi.2017.06.009","article-title":"Implications of the Gut Microbiota in Vulnerability to the Social Avoidance Effects of Chronic Social Defeat in Male Mice","volume":"66","author":"Szyszkowicz","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.3389\/fpsyt.2020.00541","article-title":"Altered Composition of Gut Microbiota in Depression: A Systematic Review","volume":"11","author":"Barandouzi","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1001\/jamapsychiatry.2021.2573","article-title":"Perturbations in Gut Microbiota Composition in Psychiatric Disorders: A Review and Meta-Analysis","volume":"78","author":"Nikolova","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.jad.2020.01.137","article-title":"Reduced Anti-Inflammatory Gut Microbiota Are Associated with Depression and Anhedonia","volume":"266","author":"Mason","year":"2020","journal-title":"J. Affect. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"17878","DOI":"10.1038\/s41598-020-74934-9","article-title":"Unravelling the Antimicrobial Action of Antidepressants on Gut Commensal Microbes","volume":"10","author":"Mottawea","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1007\/s00213-018-5006-5","article-title":"Differential Effects of Psychotropic Drugs on Microbiome Composition and Gastrointestinal Function","volume":"236","author":"Cussotto","year":"2019","journal-title":"Psychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/phar.1890","article-title":"Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort","volume":"37","author":"Flowers","year":"2017","journal-title":"Pharmacotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tanner, S.A., Zihler Berner, A., Rigozzi, E., Grattepanche, F., Chassard, C., and Lacroix, C. (2014). In Vitro Continuous Fermentation Model (PolyFermS) of the Swine Proximal Colon for Simultaneous Testing on the Same Gut Microbiota. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094123"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mottawea, W., Sultan, S., Landau, K., Bordenave, N., and Hammami, R. (2020). Evaluation of the Prebiotic Potential of a Commercial Synbiotic Food Ingredient on Gut Microbiota in an Ex Vivo Model of the Human Colon. Nutrients, 12.","DOI":"10.3390\/nu12092669"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zihler Berner, A., Fuentes, S., Dostal, A., Payne, A.N., Vazquez Gutierrez, P., Chassard, C., Grattepanche, F., de Vos, W.M., and Lacroix, C. (2013). Novel Polyfermentor Intestinal Model (PolyFermS) for Controlled Ecological Studies: Validation and Effect of PH. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077772"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110182","DOI":"10.1016\/j.pnpbp.2020.110182","article-title":"Nutritional and Therapeutic Approaches for Protecting Human Gut Microbiota from Psychotropic Treatments","volume":"108","author":"Mottawea","year":"2021","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1093\/jac\/dkx254","article-title":"A Randomized Controlled Trial of Probiotics for Clostridium Difficile Infection in Adults (PICO)","volume":"72","author":"Barker","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/19490976.2016.1138197","article-title":"Impact of Probiotic Supplements on Microbiome Diversity Following Antibiotic Treatment of Mice","volume":"7","author":"Grazul","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"20659","DOI":"10.1038\/s41598-021-00096-x","article-title":"Lactobacillus Rhamnosus and Bifidobacterium Longum Alleviate Colitis and Cognitive Impairment in Mice by Regulating IFN-\u03b3 to IL-10 and TNF-\u03b1 to IL-10 Expression Ratios","volume":"11","author":"Ma","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.ridd.2013.12.004","article-title":"The Effectiveness of Aripiprazole in the Management of Problem Behaviour in People with Intellectual Disabilities, Developmental Disabilities and\/or Autistic Spectrum Disorder\u2014A Systematic Review","volume":"35","author":"Deb","year":"2014","journal-title":"Res. Dev. Disabil."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/nature25979","article-title":"Extensive Impact of Non-Antibiotic Drugs on Human Gut Bacteria","volume":"555","author":"Maier","year":"2018","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.tibtech.2015.06.011","article-title":"Proteobacteria: Microbial Signature of Dysbiosis in Gut Microbiota","volume":"33","author":"Shin","year":"2015","journal-title":"Trends Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.chom.2010.08.004","article-title":"Enterobacteriaceae Act in Concert with the Gut Microbiota to Induce Spontaneous and Maternally Transmitted Colitis","volume":"8","author":"Garrett","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1038\/s41467-019-08812-y","article-title":"The Human Gut Firmicute Roseburia Intestinalis Is a Primary Degrader of Dietary \u03b2-Mannans","volume":"10","author":"Leth","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1038\/s41564-018-0272-x","article-title":"Interactions between Roseburia Intestinalis and Diet Modulate Atherogenesis in a Murine Model","volume":"3","author":"Kasahara","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/mp.2016.44","article-title":"Gut Microbiome Remodeling Induces Depressive-like Behaviors through a Pathway Mediated by the Host\u2019s Metabolism","volume":"21","author":"Zheng","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbi.2015.03.016","article-title":"Altered Fecal Microbiota Composition in Patients with Major Depressive Disorder","volume":"48","author":"Jiang","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1007\/s11064-018-2620-x","article-title":"Intestinal Pathology and Gut Microbiota Alterations in a Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Mouse Model of Parkinson\u2019s Disease","volume":"43","author":"Lai","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li\u015bkiewicz, P., Pe\u0142ka-Wysiecka, J., Kaczmarczyk, M., \u0141oniewski, I., Wro\u0144ski, M., B\u0105ba-Kubi\u015b, A., Skonieczna-\u017bydecka, K., Marlicz, W., Misiak, B., and Samochowiec, J. (2019). Fecal Microbiota Analysis in Patients Going through a Depressive Episode during Treatment in a Psychiatric Hospital Setting. J. Clin. Med., 8.","DOI":"10.3390\/jcm8020164"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1017\/S1751731114002584","article-title":"A Review on Prebiotics and Probiotics for the Control of Dysbiosis: Present Status and Future Perspectives","volume":"9","author":"Ducatelle","year":"2015","journal-title":"Animal"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Marzorati, M., Van den Abbeele, P., Bubeck, S.S., Bayne, T., Krishnan, K., Young, A., Mehta, D., and DeSouza, A. (2020). Bacillus Subtilis HU58 and Bacillus Coagulans SC208 Probiotics Reduced the Effects of Antibiotic-Induced Gut Microbiome Dysbiosis in An M-SHIME\u00ae Model. Microorganisms, 8.","DOI":"10.3390\/microorganisms8071028"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Arslanova, A., Tarasova, A., Alexandrova, A., Novoselova, V., Shaidullov, I., Khusnutdinova, D., Grigoryeva, T., Yarullina, D., Yakovleva, O., and Sitdikova, G. (2021). Protective Effects of Probiotics on Cognitive and Motor Functions, Anxiety Level, Visceral Sensitivity, Oxidative Stress and Microbiota in Mice with Antibiotic-Induced Dysbiosis. Life, 11.","DOI":"10.3390\/life11080764"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/ismej.2015.151","article-title":"Lactobacillus Rhamnosus GG-Supplemented Formula Expands Butyrate-Producing Bacterial Strains in Food Allergic Infants","volume":"10","author":"Sangwan","year":"2016","journal-title":"ISME J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of Short Chain Fatty Acids by the Gut Microbiota and Their Impact on Human Metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The Microbial Metabolites, Short Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.bbi.2020.03.026","article-title":"Reductions in Anti-Inflammatory Gut Bacteria Are Associated with Depression in a Sample of Young Adults","volume":"88","author":"Liu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The Treatment-Naive Microbiome in New-Onset Crohn\u2019s Disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1136\/gutjnl-2014-307649","article-title":"Identification of an Anti-Inflammatory Protein from Faecalibacterium Prausnitzii, a Commensal Bacterium Deficient in Crohn\u2019s Disease","volume":"65","author":"Maubert","year":"2016","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.immuni.2018.12.018","article-title":"The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages","volume":"50","author":"Schulthess","year":"2019","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15725","DOI":"10.1038\/s41598-017-16060-7","article-title":"Comparison of (R)-Ketamine and Lanicemine on Depression-like Phenotype and Abnormal Composition of Gut Microbiota in a Social Defeat Stress Model","volume":"7","author":"Qu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jad.2016.09.012","article-title":"Antidepressants, Antimicrobials or Both? Gut Microbiota Dysbiosis in Depression and Possible Implications of the Antimicrobial Effects of Antidepressant Drugs for Antidepressant Effectiveness","volume":"208","author":"Macedo","year":"2017","journal-title":"J. Affect. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Nikolova, V.L., Cleare, A.J., Young, A.H., and Stone, J.M. (2021). Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment. JCM, 10.","DOI":"10.3390\/jcm10040647"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s12602-012-9111-1","article-title":"Stability and Inhibitory Activity of Pediocin PA-1 Against Listeria Sp. in Simulated Physiological Conditions of the Human Terminal Ileum","volume":"4","author":"Hammami","year":"2012","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s002489900072","article-title":"Validation of a Three-Stage Compound Continuous Culture System for Investigating the Effect of Retention Time on the Ecology and Metabolism of Bacteria in the Human Colon","volume":"35","author":"Macfarlane","year":"1998","journal-title":"Microb. Ecol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, Interactive, Scalable and Extensible Microbiome Data Science Using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic Biomarker Discovery and Explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7326\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:16:28Z","timestamp":1760123788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/8\/7326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,15]]},"references-count":42,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24087326"],"URL":"https:\/\/doi.org\/10.3390\/ijms24087326","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,15]]}}}