{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:44:52Z","timestamp":1790196292899,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:sec>\n                    <jats:title>Backgroud<\/jats:title>\n                    <jats:p>Second-generation antipsychotics (SGAs) are widely used in the treatment of schizophrenia, however, growing concerns have emerged regarding their adverse effects on glucose and lipid metabolism. This study aimed to investigate the potential mechanisms underlying SGA-induced disturbances in glucose and lipid metabolism by integrating gut microbiota profiling with metabolomic analysis, thereby providing a scientific basis for future clinical interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A self-controlled before-after study was conducted on subjects who were initially medication-free (pre-medication group) and subsequently initiated on second-generation antipsychotics for 3 months (post-medication group). Anthropometric measurements\u2014including waist circumference, hip circumference, body weight\u2014as well as fasting blood samples (for assessment of glucose, insulin, C peptide, blood lipid) and stool samples were collected at baseline and after three months of treatment. Gut microbiota composition and fecal metabolomic profiles were analyzed using high-throughput sequencing and mass spectrometry\u2013based approaches, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Firstly, Gut microbial diversity differed significantly between groups. At genus level, the abundances of\n                      <jats:italic>Escherichia<\/jats:italic>\n                      and\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      were increased significantly in the post-medication patients, while the abundances of\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      and\n                      <jats:italic>Blautia<\/jats:italic>\n                      were decreased. Metabolomic analysis revealed decreased levels of oleamide and stearamide in the post-medication group, which exhibited a negative correlation with the abundance of\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      . Additionally, the arginine and proline metabolic pathway, D-amino acid metabolic pathway, and arginine biosynthesis pathway were also altered in this group. Ornithine was identified as a key player in these three differential metabolic pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, first-time exposure to second-generation antipsychotics in patients with schizophrenia is associated with disturbances in glucose and lipid metabolism, which appear to be closely linked to SGA-induced perturbations in gut microbiota composition and their associated metabolic profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2025.1722760","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:06:56Z","timestamp":1765202816000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["First exposure to second-generation antipsychotics alters gut microbiota and metabolic profiles in patients 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