{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:49:28Z","timestamp":1785422968402,"version":"3.56.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                      (\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      ) is a mucin-degrading commensal bacterium with established roles in maintaining intestinal homeostasis and modulating host immune responses. However, its therapeutic potential and mechanisms in chronic spontaneous colitis remain incompletely defined. Interleukin-10 knockout (IL-10\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      ) mice are a well-established model of spontaneous colitis due to impaired anti-inflammatory cytokine signaling and disrupted immune regulation. In this study, we aimed to determine whether\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      and its culture-derived supernatant could ameliorate intestinal inflammation in IL-10\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We administered\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      or its culture supernatant (\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      supernatant [A.m-SN]) to IL-10\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice and monitored disease progression over 30 days. Clinical assessments included body weight, disease activity index (DAI), colon length, histopathology, and endoscopy. Tight junction proteins (zonula occludens-1 [ZO-1] and Occludin) and colonic messenger ribonucleic acid levels of pro- and anti-inflammatory cytokines were evaluated. Gut microbiota composition was assessed using 16S ribosomal deoxyribonucleic acid sequencing, and untargeted metabolomic profiling was performed on the culture medium to identify potential anti-inflammatory components.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mice treated with\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      or A.m-SN showed significantly reduced colitis severity, including reduced body weight loss, lower DAI, preserved colon length, and improved histological scores. Immunofluorescence revealed increased expression of ZO-1 and Occludin in colonic tissues. Pro-inflammatory cytokines (tumor necrosis factor-\u03b1, IL-6, IL-17, IL-1\u03b2, and interferon-\u03b3) were downregulated, while anti-inflammatory cytokines (IL-4, transforming growth factor-\u03b2, and IL-22) were upregulated in treated groups. Gut microbiota analysis showed partial restoration of microbial diversity and structure. Metabolomic profiling identified distinct signatures in A.m-SN, with bioactive molecules such as adenosine and tryptophan derivatives implicated in the anti-inflammatory effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The culture supernatant of\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      alleviated spontaneous colitis in IL-10\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/\n                      <jats:sup>\u2212<\/jats:sup>\n                      mice by suppressing pro-inflammatory cytokines, enhancing anti-inflammatory mediators, and strengthening epithelial barrier function. Metabolomic profiling identified candidate bioactive components, including adenosine and tryptophan derivatives, supporting its potential as a postbiotic intervention for inflammatory bowel disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1693007","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T06:27:10Z","timestamp":1763360830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Akkermansia muciniphila and its culture supernatant ameliorate colitis in interleukin-10 knockout mice via gut barrier and immune 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