{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T14:46:43Z","timestamp":1772981203602,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":300,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["Pediatric Diabetes"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether human leukocyte antigens (HLAs) influence gut microbiota composition and contributes to delayed type 1 diabetes mellitus (T1DM) onset in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter cross\u2010sectional study included 106 newly diagnosed pediatric T1DM patients (age &lt;18 years) and 69 healthy controls from nine Chinese cities. Gut microbiota was profiled via whole\u2010metagenome shotgun sequencing, and HLA alleles were genotyped by PCR sequence\u2010based typing. Participants were stratified by HLA\u2010risk scores. Statistical analyses included \u03b1\/\u03b2\u2010diversity metrics, linear discriminant analysis effect size analysis (LEfSe), and Spearman correlation adjusted for confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Principal coordinates analysis (PCoA) exposed discernible disparities in gut microbiota structures within the high\u2010HLA\u2010risk T1DM cohort relative to both high\u2010 and low\u2010HLA\u2010risk control groups (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0562,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003 and\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0343,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003). HLA\u2010C\n                      <jats:sup>\u2217<\/jats:sup>\n                      0304 carriers exhibited delayed T1DM onset compared to noncarriers (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.225,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.017). High\u2010HLA\u2010risk T1DM patients showed distinct microbiota divergence from controls (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.0562,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.003), driven by reduced Lachnospiraceae and\n                      <jats:italic>Blautia<\/jats:italic>\n                      (butyrate producers) in noncarriers. Conversely, HLA\u2010C\n                      <jats:sup>\u2217<\/jats:sup>\n                      0304\u2010positive T1DM patients had enriched\n                      <jats:italic>Blautia<\/jats:italic>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.005) and Lachnospiraceae (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.039), alongside lower opportunistic pathogens (\n                      <jats:italic>Citrobacter<\/jats:italic>\n                      ;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). High\u2010HLA\u2010risk patients also displayed lower fasting C\u2010peptide levels than low\u2010risk counterparts (0.19\u2009\u00b1\u20090.14 vs. 0.26\u2009\u00b1\u20090.19\u2009\u00b5g\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.029).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates that specific HLA class I subtypes (e.g., C\n                      <jats:sup>\u2217<\/jats:sup>\n                      0304) may modulate T1DM onset through selective enrichment of beneficial gut microbiota. Elucidating the mechanisms by which HLA variants regulate mucosal immunity and coordinate HLA\u2010microbiota\u2010immune interactions holds significant potential for developing targeted interventions against T1DM pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/pedi\/3013063","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:52:35Z","timestamp":1761720755000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HLA\u2010C\n                    <i>\u2009<\/i>\n                    <sup>\u2217<\/sup>\n                    0304 Associates With Beneficial Gut Microbiota and Later Onset of Type 1 Diabetes in Pediatric 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