{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:37Z","timestamp":1787120857193,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Graves\u2019 disease (GD) represents a typical autoimmune thyroid disease triggered by thyroid-stimulating autoantibodies. Accumulating studies have verified the close correlation between intestinal microecology and GD progression, with\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      prominently implicated, yet the specific molecular mechanisms underlying this association remain elusive. This study aimed to explore the regulatory effects of\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      on GD development via the CD40-NF-\u03baB signaling cascade and sodium\/iodide symporter (NIS) modulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinically, fecal specimens from GD patients were recruited before and after iodine-131 (\n                      <jats:sup>131<\/jats:sup>\n                      I) therapy to characterize dynamic changes in intestinal\n                      <jats:italic>Bifidobacterium<\/jats:italic>\n                      abundance.\n                      <jats:italic>In vitro<\/jats:italic>\n                      cellular assays were conducted on human thyroid cells stimulated with\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      , followed by detection of cell proliferative activity, CD40-NF-\u03baB pathway activity and NIS protein expression.\n                      <jats:italic>In vivo<\/jats:italic>\n                      GD mouse models were administered with\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      intervention, and subsequent assessments included thyroid and colonic histopathological changes and gut microbial profiling. The expression levels of key proteins associated with the CD40-NF-\u03baB pathway and NIS were also quantified in thyroid and colon tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Clinical results demonstrated that\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      abundance was significantly higher in GD patients prior to\n                      <jats:sup>131<\/jats:sup>\n                      I treatment and markedly decreased after therapy.\n                      <jats:italic>In vitro<\/jats:italic>\n                      ,\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      treatment facilitated thyroid cell proliferation, elevated NIS expression and activated the CD40-NF-\u03baB signaling in a dose-dependent manner. In animal models,\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      supplementation aggravated hyperthyroidism, thyroid hyperplasia and intestinal inflammatory injuries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Mechanistically,\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      drove CD40 and NIS upregulation through triggering NF-\u03baB pathway activation. Collectively,\n                      <jats:italic>Bifidobacterium adolescentis<\/jats:italic>\n                      exacerbates GD pathogenesis by activating the CD40-NF-\u03baB signaling axis and modulating thyroid NIS expression. This work reveals a novel microbial regulatory mechanism of GD, offering a promising theoretical basis for developing gut microbiota-targeted therapeutic strategies for GD treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1894196","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:46:40Z","timestamp":1787118400000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Bifidobacterium-regulated NIS expression with the CD40-NF-\u03baB pathway in Graves\u2019 disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Kexin","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Wan","sequence":"additional","affiliation":[{"name":"Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Institute of One Health, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Ying","sequence":"additional","affiliation":[{"name":"Wenzhou Medical University Renji College, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengwei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Li","sequence":"additional","affiliation":[{"name":"Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Institute of One Health, Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, The First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2942","DOI":"10.4049\/jimmunol.167.5.2942","article-title":"Prevention of experimental autoimmune encephalomyelitis in the common marmoset (Callithrix jacchus) using a chimeric antagonist monoclonal antibody against human CD40 is associated with altered B cell responses","volume":"167","author":"Boon","year":"2001","journal-title":"J. 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