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However, the underlying mechanism remains unclear. This study explores the impact of depression and related intestinal microbiota on immune\u2010mediated hepatitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We assessed depression in 260 AIH patients receiving 2\u2010year standardized treatment and 173 healthy controls. In mice, depressive\u2010like behaviors were induced by chronic unpredictable mild stress (CUMS), and immune\u2010mediated hepatitis was induced by intravenous injection of concanavalin A (ConA). Fecal microbiota transplantation (FMT) was performed using samples from patients with major depressive disorder (MDD) and controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Depression was common in patients with AIH (106\/260, 40.8%) and was associated with cirrhosis. Compared with nondepressed AIH patients, those with depression showed exacerbated intestinal barrier dysfunction and hepatic NLR family pyrin domain containing 3 (NLRP3) inflammasome overactivation. In the ConA\u2010induced hepatitis model, CUMS exposure aggravated these abnormalities, which were then attenuated by mirtazapine. Furthermore, mice colonized with MDD microbiota exhibited greater intestinal barrier disruption and hepatic NLRP3 inflammasome overactivation than those colonized with control microbiota. Notably, gut\u2010derived\n                      <jats:italic>Lactococcus formosensis<\/jats:italic>\n                      , isolated from the livers of MDD microbiota\u2010colonized mice, could translocate to the liver and induce hepatic NLRP3 inflammasome overactivation. In addition, vaccination against\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>L. formosensis<\/jats:italic>\n                      <\/jats:styled-content>\n                      prevented translocation and alleviated liver injury in monocolonized mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Depression aggravates immune\u2010mediated hepatitis through disruption of intestinal barrier integrity and overactivation of hepatic NLRP3 inflammasome. Gut\u2010derived\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>L. formosensis<\/jats:italic>\n                      <\/jats:styled-content>\n                      could translocate to the liver and induce liver injury in mice. This study provides the necessity of screening for depression in patients with AIH.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70743","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T09:42:03Z","timestamp":1767865323000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Depression Aggravates Immune\u2010Mediated Hepatitis Through\n                    <scp>NLRP3<\/scp>\n                    Overactivation Induced by Intestinal Microbiota"],"prefix":"10.1002","volume":"32","author":[{"given":"Simin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Tianjin Medical University General Hospital  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology 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