{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:37:07Z","timestamp":1775032627006,"version":"3.50.1"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Akkermansia muciniphila (AKK) is a potential probiotic. Our previous studies have shown that it could alleviate depressive-like behaviors (DLBs) in mice by inhibiting neuroinflammation in brain. To further explore its antidepressant effect, this study focused on the effects of AKK on the metabolic activities in gut-brain axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After chronic restraint stress (CRS) depression model was successfully built, AKK was used as intervention method for 3\u00a0weeks. The gut microbiome in feces and two intestinal permeability proteins in colon (Claudin-1, Occludin) were measured, and the metabolites in feces, colon, liver, and prefrontal cortex were also measured. In addition, two inflammation-related factors in hippocampus (Free fatty acid receptors 3 (FFAR3), phosphorylated NF-\u03baB p65 (p-p65)) were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AKK was successfully colonized in gut of chronic restraint stress (CRS) mice. The DLBs in CRS mice receiving AKK (CRS + AKK) were significantly improved, along with the improved gut microbiome. Both Claudin-1 and Occludin in colon were significantly increased in CRS + AKK mice compared to CRS mice receiving phosphate buffer saline (PBS) (CRS + p). Metabolomics analysis indicated that AKK could significantly improve the changed lipids and lipid-like molecules in gut-brain axis of CRS mice; and function analysis using differential metabolites showed that AKK could significantly improve the disordered glycerophospholipid metabolism in feces, colon, liver, and prefrontal cortex of CRS mice. Additionally, we found that FFAR3 and phosphorylated NF-\u03baB p65 were increased and decreased, respectively, in hippocampus of CRS + AKK mice compared to CRS + p mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggested that AKK might improve the disturbances of gut microbiome, intestinal permeability, host\u2019s lipid metabolism and inflammation levels in hippocampus. Glycerophospholipid metabolism in gut-brain axis might be the important mediator in the process of AKK producing antidepressants effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1790866","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:43:23Z","timestamp":1775022203000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Fei","family":"He","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunjie","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaolin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Health Commission Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Neurology, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.jad.2014.09.020","article-title":"Risk factors for treatment resistance in unipolar depression: a systematic review","volume":"171","author":"Bennabi","year":"2015","journal-title":"J. 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