{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:29:45Z","timestamp":1792096185214,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging\u2010related metabolic decline, particularly impaired glucose tolerance, represents a growing challenge in aging populations. Probiotics are promising modulators of host metabolism; however, how sex differences influence their efficacy in mitigating metabolic aging remains poorly understood. Here, we administered\n                    <jats:italic>Lactiplantibacillus plantarum<\/jats:italic>\n                    AS21 to naturally aged male and female mice for 6\u2009months. We observed a pronounced sexual dimorphism in metabolic decline, with aged males exhibiting more severe glucose intolerance than females. Concurrently, circulating citrulline levels were depleted in males but elevated in females. AS21 intervention significantly ameliorated glucose intolerance in aged males, while exerting minimal effects on metabolically stable females. Microbiota analysis revealed that AS21 reshaped the mucosa\u2010associated microbial communities in males, an effect accompanied by increased abundance of microbial citrulline biosynthesis genes (\n                    <jats:italic>argF<\/jats:italic>\n                    ,\n                    <jats:italic>argI<\/jats:italic>\n                    ) and restoration of circulating citrulline. In contrast, females maintained stable metabolic and citrulline profiles alongside limited microbial alterations. Furthermore, direct citrulline supplementation recapitulated these metabolic benefits, improving glucose tolerance, enhancing glucose\u2010stimulated insulin secretion (GSIS), and stimulating glucagon\u2010like peptide\u20101 (GLP\u20101) release. Collectively, these findings demonstrate that AS21 alleviates age\u2010related glucose dysregulation in male mice\u2014a benefit closely associated with the restoration of microbiota\u2010driven citrulline metabolism. This highlights its potential as a sex\u2010specific, microbiota\u2010targeted strategy for managing metabolic aging.\n                  <\/jats:p>","DOI":"10.1111\/acel.70662","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T03:18:35Z","timestamp":1786677515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>Lactiplantibacillus plantarum<\/i>\n                    AS21 Attenuates Sex\u2010Biased Glucose Intolerance in Aging Mice via Gut Mucosal Microbiota\u2010Derived Citrulline"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1073-0926","authenticated-orcid":false,"given":"Mengya","family":"Jia","sequence":"first","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5243-4842","authenticated-orcid":false,"given":"Mengyan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2376-3560","authenticated-orcid":false,"given":"Hu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiling","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Dou","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8224-7693","authenticated-orcid":false,"given":"Chaorui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Ishaq","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3609-3630","authenticated-orcid":false,"given":"Xiaoying","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1062-2298","authenticated-orcid":false,"given":"Zitong","family":"Ding","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5587-3920","authenticated-orcid":false,"given":"Xusheng","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Sciences Lanzhou University  Lanzhou Gansu Province China"},{"name":"Probiotics and Life Health Institute Lanzhou University  Lanzhou Gansu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2024.102020"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13937"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.01.013"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010024\u201000996\u20108"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14334"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13269"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010publhealth\u2010060222\u2010023417"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010021\u201000642\u20100"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564\u2010025\u201001932\u2010w"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.131733"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70130"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2048300"},{"key":"e_1_2_10_15_1","unstructured":"International Diabetes Federation.2025.\u201cIDF Diabetes Atlas 11th Edition.\u201dhttps:\/\/diabetesatlas.org\/resources\/idf\u2010diabetes\u2010atlas\u20102025."},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319902"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2024.2362265"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.011"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.04.004"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1fo03538j"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.12.006"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2017.10.009"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101798"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.4c00507"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2136467"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2025.128317"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2020.02.005"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.09.040"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010023\u201000960\u2010y"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14028"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxab279"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168\u2010024\u201001750\u2010y"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c03818"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2025.111593"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads4957"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889\u2010022\u201013759\u20109"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153268"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010020\u201000014\u20102"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.11.017"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13668\u2010020\u201000307\u20103"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70662","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70662","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70662","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:11:19Z","timestamp":1787321479000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/acel.70662"],"URL":"https:\/\/doi.org\/10.1111\/acel.70662","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70662"}}