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This study investigated the effects of ARI on splenic microbiota composition and splenic neuroendocrine and immune responses in an animal model of PTSD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were exposed to the single prolonged stress (SPS) paradigm to induce a PTSD-like phenotype and treated intraperitoneally with vehicle or ARI for 28 days. Anxiety-like behavior was assessed using the elevated plus maze. Splenic microbiota and gene expression were quantified by real-time PCR in isolated splenocytes following ex vivo stimulation with lipopolysaccharide or phorbol 12-myristate 13-acetate (PMA)\/ionomycin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SPS and SPS\u2009+\u2009ARI reduced the abundance of the phylum\n                      <jats:italic>Bacteroidetes<\/jats:italic>\n                      . SPS increased\n                      <jats:italic>\u03b3\/\u03b4-Proteobacteria<\/jats:italic>\n                      and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      abundance, effects attenuated by ARI. The presence of specific splenic bacteria correlated with anxiety-like behavior. While lipopolysaccharide-induced responses were unaffected, splenocytes from SPS-exposed rats exhibited increased expression of Th1- and Th17-related genes after PMA\/ionomycin stimulation; this effect was reversed by ARI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ARI modulates SPS-induced alterations in splenic microbiota and attenuates heightened Th1- and Th17-associated responses, thereby contributing to the restoration of immune balance. Our findings underscore involvement of the gut\u2013spleen\u2013brain axis in PTSD pathogenesis and immunosuppressive\/ microbiota-modulating effects of aripiprazole on splenic immune cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s43440-026-00882-2","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:07:37Z","timestamp":1784534857000},"page":"1102-1118","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aripiprazole modulates splenic microbiota and immune response elicited by single prolonged stress in rats"],"prefix":"10.1007","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0417-8984","authenticated-orcid":false,"given":"Peter","family":"Vargovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-7040","authenticated-orcid":false,"given":"Andrej","family":"Tillinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5280-7805","authenticated-orcid":false,"given":"Lubica","family":"Horvathova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6796-5831","authenticated-orcid":false,"given":"Lila","family":"Dziewiczova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2144-0534","authenticated-orcid":false,"given":"Jana","family":"Osacka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"882_CR1","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/npp.2016.146","volume":"42","author":"V Michopoulos","year":"2017","unstructured":"Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. 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