{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:27:30Z","timestamp":1787027250392,"version":"build-2736575974"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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>Background<\/jats:title>\n                    <jats:p>\n                      Major depressive disorder (MDD) is a common and heterogeneous mental illness with an unclear pathogenesis and often suboptimal treatment outcomes.\n                      <jats:italic>Astragalus<\/jats:italic>\n                      polysaccharide (APS) has shown potential antidepressant effects and may serve as a functional food; however, its impact on the gut microbiota and metabolome in MDD remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using an\n                      <jats:italic>in vitro<\/jats:italic>\n                      fermentation model coupled with 16S rRNA sequencing and targeted metabolomics, we characterized the gut microbial composition and neurotransmitter metabolites in fecal samples from 15 MDD patients and 15 healthy subjects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MDD samples exhibited elevated\n                      <jats:italic>Fusobacteriaecae<\/jats:italic>\n                      and\n                      <jats:italic>Eggerthellaceae<\/jats:italic>\n                      , reduced levels of\n                      <jats:italic>Eubacterium hallii<\/jats:italic>\n                      ,\n                      <jats:italic>Faecalibacterium<\/jats:italic>\n                      , and\n                      <jats:italic>Ruminococcus<\/jats:italic>\n                      , and higher concentrations of glutamine (Gln) and glutamate (Glu). APS fermentation significantly increased\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      and\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      while decreasing\n                      <jats:italic>Eubacterium hallii<\/jats:italic>\n                      and\n                      <jats:italic>Bilophila<\/jats:italic>\n                      , without increasing the total gas volume, CO\n                      <jats:sub>2<\/jats:sub>\n                      , and H\n                      <jats:sub>2<\/jats:sub>\n                      S production. Additionally, beneficial metabolites were elevated in MDD samples after APS addition, including glutamine (Gln), \u03b3-aminobutyric acid (GABA), dopamine (DA), and 5-hydroxytryptophan (5-HTP). The increase in GABA among healthy subjects was more significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings indicate that MDD is associated with disruptions in gut microbiota and Glu\/GABA metabolism. When APS are applied directly to the colon, they may mitigate these disruptions by modulating microbial composition and key neuroactive metabolites, thereby influencing the central nervous system via the gut-brain axis. This effect appears to be more pronounced in healthy individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.medicalresearch.org.cn<\/jats:ext-link>\n                      , identifier MR-33-25-010733.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1752933","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T07:04:04Z","timestamp":1772003044000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of in vitro fermentation of Astragalus polysaccharide on gut microbiota and neurotransmitter metabolites in patients with major depressive disorder"],"prefix":"10.3389","volume":"17","author":[{"given":"Chen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wei","family":"Mi","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huo-Wang","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Bin","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Qiong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xin","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Lang","family":"Fu","sequence":"additional","affiliation":[{"name":"Rehabilitation Department, The People\u2019s Hospital of Ningbo Haishu District","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qiong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Zhejiang Academy of Agricultural Sciences","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Xin","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Psychosomatic Medicine, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(21)00251-0","article-title":"Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study","volume":"8","author":"Lu","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03047-0","article-title":"Antidepressant actions of ketamine engage cell-specific translation via eIF4E","volume":"590","author":"Aguilar-Valles","year":"2021","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.eng.2019.07.026","article-title":"Targeting gut microbiota dysbiosis: Potential intervention strategies for neurological disorders","volume":"6","author":"Wu","year":"2020","journal-title":"Eng"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2020.101943","article-title":"The gut microbiota in anxiety and depression - 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