{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:01:56Z","timestamp":1785132116455,"version":"3.55.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]}],"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                      Inflammatory bowel disease (IBD) is characterized by marked clinical heterogeneity, reflecting complex interactions between host genetics, environmental exposures, and the gut microbiome. Although over 300 genetic risk loci have been identified, these account for only a fraction of disease variance, highlighting the importance of gene\u2013environment interactions. ADAM-like Decysin-1 (ADAMDEC1) is a gastrointestinal-restricted metalloprotease implicated in mucosal repair and immune regulation, with reduced expression reported in IBD. While\n                      <jats:italic>Adamdec1<\/jats:italic>\n                      -deficient mice exhibit increased susceptibility to colitis, the mechanisms underlying phenotypic variability remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To dissect genetic and environmental contributions to colitis severity, C57BL\/6J wild-type (WT) and\n                      <jats:italic>\n                        Adamdec1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice were co-housed in two distinct environments and subjected to dextran sodium sulfate (DSS)-induced colitis. Disease severity was assessed by weight loss, immune cell infiltration, and transcriptional profiling of inflammatory and epithelial repair markers using flow cytometry and qPCR. Gut microbiome composition was analyzed from fecal samples collected following extended co-housing to evaluate environment-driven microbial differences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Environmental factors exerted a stronger influence than genotype on gut microbiome composition. WT mice displayed consistent inflammatory and transcriptional responses to DSS across environments, whereas\n                      <jats:italic>Adamdec1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited marked cage-dependent variability, ranging from severe colitis to a mild, WT-like phenotype. Severe disease in\n                      <jats:italic>Adamdec1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice was associated with enhanced neutrophil recruitment, increased CD11b expression, altered monocyte\/macrophage activation, impaired epithelial proliferation, and disrupted stem cell\u2013associated gene expression. These phenotypic differences correlated with distinct microbiome profiles indicating genotype-dependent microbial pathogenicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that loss of\n                      <jats:italic>Adamdec1<\/jats:italic>\n                      creates a state of heightened sensitivity to environmental and microbiome related factors, in which gut microbial composition correlates with differences in inflammatory and epithelial outcomes during colitis. This study identifies a gene\u2013environment\u2013microbiome axis associated with phenotypic variability in intestinal inflammation and provides mechanistic insight into the heterogeneity of IBD. Targeting environmentally driven microbial modifiers may represent a promising strategy for personalized intervention in genetically susceptible individuals.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1824007","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:41:31Z","timestamp":1785130891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Environment shapes gut microbiome and determines susceptibility to DSS-colitis in Adamdec1-\/- mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Tomoko","family":"Kumagai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Whipps Cross University Hospital, Barts Health NHS Trust","place":["London, United Kingdom"]},{"name":"Department of Microbial Diseases, University College London (UCL) Eastman Dental Institute, University College London","place":["London, 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