{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:44:26Z","timestamp":1782805466951,"version":"3.54.5"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Council of Saint Joseph University of Beirut and by Lallemand Health Solutions","award":["NCT05646784"],"award-info":[{"award-number":["NCT05646784"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background\/Objectives: Major depressive disorder (MDD) is increasingly recognized as involving inflammation and the microbiota\u2013gut\u2013brain axis. Few studies have simultaneously assessed systemic inflammatory markers and gut microbiota composition within the same cohort while accounting for metabolic confounders. Moreover, data from Middle Eastern and North African (MENA) populations remain limited, restricting our understanding of how diet may influence neuroimmune\u2013microbiome interactions in depression. This study aimed to investigate associations between MDD, systemic inflammatory markers, and gut microbiota composition in Lebanese adults. To our knowledge, this is the first study of its kind in Lebanon, as well as in the MENA region. Methods: In this cross-sectional case\u2013control study, we examined circulating inflammatory markers and gut microbial profiles in 46 adults with DSM-5-confirmed MDD and 25 healthy controls. Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) were measured, and the gut microbiota composition was characterized using 16S rRNA gene sequencing. Multivariable models were adjusted for age, sex, body mass index (BMI), Mediterranean diet adherence, and fluoxetine exposure. Results: Depression status was not independently associated with CRP or IL-6 after adjustment, whereas BMI emerged as a significant determinant of systemic inflammation. At the genus level, MDD was associated with the enrichment of Dorea, Lachnoclostridium, Collinsella, Bilophila, and Klebsiella and the depletion of Christensenella, Mitsuokella, and Victivallis, independent of inflammatory biomarkers. Alpha diversity did not differ between groups, while beta diversity showed modest metric-dependent differences, primarily driven by presence\/absence-based measures. Conclusions: Specific microbial taxa may contribute to gut\u2013brain signaling pathways implicated in MDD and systemic inflammation. Further longitudinal and mechanistic studies are required to clarify causal interactions within inflammation\u2013microbiome networks in MDD.<\/jats:p>","DOI":"10.3390\/brainsci16070681","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:58:04Z","timestamp":1782799084000},"page":"681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Inflammatory and Gut Microbial Signatures in Major Depressive Disorder: A Case\u2013Control Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Nour","family":"Dabboussi","sequence":"first","affiliation":[{"name":"Laboratory of Research in Physiology and Pathophysiology, Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1107 2020, Lebanon"},{"name":"Laboratoire Microbiologie Sant\u00e9 et Environnement (LMSE), Doctoral School of Science & Technology, Faculty of Public Health, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-7518","authenticated-orcid":false,"given":"Esp\u00e9rance","family":"Debs","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Arts and Sciences, University of Balamand, Tripoli P.O. Box 100, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-8381","authenticated-orcid":false,"given":"Marc","family":"Bouji","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Saint Joseph University of Beirut, Beirut 1104 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7266-9795","authenticated-orcid":false,"given":"Raymond","family":"Kassab","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, H\u00f4tel-Dieu de France Hospital, Saint-Joseph University of Beirut, Beirut P.O. Box 11-5076, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-4755","authenticated-orcid":false,"given":"Rami","family":"Bou Khalil","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, H\u00f4tel-Dieu de France Hospital, Saint-Joseph University of Beirut, Beirut P.O. Box 11-5076, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2935-2611","authenticated-orcid":false,"given":"Nassim","family":"Fares","sequence":"additional","affiliation":[{"name":"Laboratory of Research in Physiology and Pathophysiology, Faculty of Medicine, Saint Joseph University of Beirut, Beirut 1107 2020, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9633-1290","authenticated-orcid":false,"given":"Rayane","family":"Rafei","sequence":"additional","affiliation":[{"name":"Laboratoire Microbiologie Sant\u00e9 et Environnement (LMSE), Doctoral School of Science & Technology, Faculty of Public Health, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.neuron.2014.01.027","article-title":"The Genetics of Major Depression","volume":"81","author":"Flint","year":"2014","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111056","DOI":"10.1016\/j.brainresbull.2024.111056","article-title":"Balancing the Mind: Toward a Complete Picture of the Interplay between Gut Microbiota, Inflammation and Major Depressive Disorder","volume":"216","author":"Dabboussi","year":"2024","journal-title":"Brain Res. 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