{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:56:22Z","timestamp":1791410182841,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T00:00:00Z","timestamp":1723507200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      We aimed to investigate whether alpha\u2010galactosylceramide (\u03b1\u2010GalCer)\u2010producing\n                      <jats:italic>Bacteroides fragilis<\/jats:italic>\n                      could induce natural killer T (NKT) cells in nonobese diabetic (NOD)\u00a0mice and reduce their diabetes incidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Five\u2010week\u2010old female NOD mice were treated orally with\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      , and islet pathology and diabetes onset were monitored. Immune responses were analyzed by flow cytometry and multiplex technology. Effects of ultraviolet (UV)\u2010killed \u03b1\u2010GalCer\u2010producing\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      and their culture medium on invariant NKT (iNKT) cells were tested ex vivo on murine splenocytes, and the immunosuppressive capacity of splenocytes from\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      \u2010treated NOD mice were tested by adoptive transfer to nonobese diabetic\/severe combined immunodeficiency (NOD\/SCID) mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      reduced the diabetes incidence from 69% to 33% and the percent of islets with insulitis from 40% to 7%, which doubled the serum insulin level compared with the vehicle\u2010treated control mice. Furthermore, the early treatment reduced proinflammatory mediators in the serum, whereas the proportion of CD4\n                      <jats:sup>+<\/jats:sup>\n                      NKT cell population was increased by 33%.\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      growth media stimulated iNKT cells and anti\u2010inflammatory M2 macrophages ex vivo in contrast to UV\u2010killed bacteria, which had no effect, strongly indicating an \u03b1\u2010GalCer\u2010mediated effect. Adoptive transfer of splenocytes from\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      \u2010treated NOD mice induced a similar diabetes incidence as splenocytes from untreated NOD mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      induced iNKT cells and M2 macrophages and reduced type 1 diabetes in NOD mice. The protective effect seemed to be more centered on gut\u2013pancreas interactions rather than a systemic immunosuppression.\n                      <jats:italic>B. fragilis<\/jats:italic>\n                      should be considered for probiotic use in individuals at risk of developing type 1 diabetes.\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jdb13593-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1753-0407.13593","type":"journal-article","created":{"date-parts":[[2024,8,13]],"date-time":"2024-08-13T09:16:39Z","timestamp":1723540599000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Probiotic treatment with viable\n                    <scp>\u03b1\u2010galactosylceramide<\/scp>\n                    \u2010producing\n                    <i>Bacteroides fragilis<\/i>\n                    reduces diabetes incidence in female nonobese diabetic mice"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-385X","authenticated-orcid":false,"given":"Camilla H. F.","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3021-8057","authenticated-orcid":false,"given":"Danica","family":"Jozipovic","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line F.","family":"Zachariassen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis S.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Food Science, Faculty of Science University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel K.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences University of Copenhagen  Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-7423","authenticated-orcid":false,"given":"Karsten","family":"Buschard","sequence":"additional","affiliation":[{"name":"Department of Pathology The Bartholin Institute, Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2904"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5343.1626"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.10.5005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.5.1369"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001610"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1521\u20104141(199906)29:06<2014::Aid\u2010immu2014>3.0.Co;2\u2010g"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261226"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.3.313"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121169698"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251531798"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.10.1831"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.7.1047"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901\u20101052"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901\u20101057"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1900\/rds.2012.9.251"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201078404\u20100"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502465"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2020.113285"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242462"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.650621"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010019\u20104910\u20105"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.112.172361"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.1257"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2006.03172.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010009\u20101626\u2010y"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07336"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201033656\u20104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40200\u2010022\u201001006\u20102"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci72334"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3047574"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1848158"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2019.108590"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19\u20100211"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909122107"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwu117"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.29797"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101390"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251\u2010016\u20100930\u20101"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037771"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011908"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1266"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1106654"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141751"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105948"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.3.1196"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343910"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20107613(02)00473\u20109"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2015.04.001"}],"container-title":["Journal of Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1753-0407.13593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T15:29:49Z","timestamp":1724340589000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1753-0407.13593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/1753-0407.13593"],"URL":"https:\/\/doi.org\/10.1111\/1753-0407.13593","archive":["Portico"],"relation":{},"ISSN":["1753-0393","1753-0407"],"issn-type":[{"value":"1753-0393","type":"print"},{"value":"1753-0407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"2023-12-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13593"}}